<?xml version="1.0" encoding="UTF-8"?>

<!--XBRL Document Created with the Workiva Platform-->
<!--Copyright 2025 Workiva-->
<!--r:dfbcc541-6520-4da2-b173-8ab0d8d03b58,g:4d673d8c-3e41-45e4-aa9b-a0892b14ac29-->
<link:linkbase xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd">
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/all" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#all"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#hypercube-dimension"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-default"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-domain"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/domain-member" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#domain-member"/>
  <link:roleRef roleURI="http://www.exagen.com/role/UnauditedCondensedStatementsofStockholdersEquity" xlink:type="simple" xlink:href="exdx-20250331.xsd#UnauditedCondensedStatementsofStockholdersEquity"/>
  <link:definitionLink xlink:role="http://www.exagen.com/role/UnauditedCondensedStatementsofStockholdersEquity" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_acc0ba6c-8ca5-49a6-b3bd-540c59b1e910" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementTable_2a2b59a2-068d-405f-b8ec-8e2f60b8ed33" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StatementTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_acc0ba6c-8ca5-49a6-b3bd-540c59b1e910" xlink:to="loc_us-gaap_StatementTable_2a2b59a2-068d-405f-b8ec-8e2f60b8ed33" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementEquityComponentsAxis_609f82a3-d747-43d5-8904-b49295467cfd" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StatementEquityComponentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_2a2b59a2-068d-405f-b8ec-8e2f60b8ed33" xlink:to="loc_us-gaap_StatementEquityComponentsAxis_609f82a3-d747-43d5-8904-b49295467cfd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_609f82a3-d747-43d5-8904-b49295467cfd_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_609f82a3-d747-43d5-8904-b49295467cfd" xlink:to="loc_us-gaap_EquityComponentDomain_609f82a3-d747-43d5-8904-b49295467cfd_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_522645b1-e559-401e-ba55-47c707a19362" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_609f82a3-d747-43d5-8904-b49295467cfd" xlink:to="loc_us-gaap_EquityComponentDomain_522645b1-e559-401e-ba55-47c707a19362" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockMember_8a095c29-0e40-401b-b9b6-edc8a12f15ec" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_522645b1-e559-401e-ba55-47c707a19362" xlink:to="loc_us-gaap_CommonStockMember_8a095c29-0e40-401b-b9b6-edc8a12f15ec" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdditionalPaidInCapitalMember_8526b7d3-ed61-4762-80d6-fedd77ae5203" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AdditionalPaidInCapitalMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_522645b1-e559-401e-ba55-47c707a19362" xlink:to="loc_us-gaap_AdditionalPaidInCapitalMember_8526b7d3-ed61-4762-80d6-fedd77ae5203" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetainedEarningsMember_25d5b078-b716-4510-aa47-81d78c9c3ce8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RetainedEarningsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_522645b1-e559-401e-ba55-47c707a19362" xlink:to="loc_us-gaap_RetainedEarningsMember_25d5b078-b716-4510-aa47-81d78c9c3ce8" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_a0cc4973-bb04-4bbc-97a0-e531b27618c4" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncreaseDecreaseInStockholdersEquityRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_acc0ba6c-8ca5-49a6-b3bd-540c59b1e910" xlink:to="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_a0cc4973-bb04-4bbc-97a0-e531b27618c4" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockSharesOutstanding_f85a2861-6d2c-4744-ad98-2d2f330506d4" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CommonStockSharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_a0cc4973-bb04-4bbc-97a0-e531b27618c4" xlink:to="loc_us-gaap_CommonStockSharesOutstanding_f85a2861-6d2c-4744-ad98-2d2f330506d4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_1dff760b-f41a-42f8-ac38-6ebaebbfcfc3" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockholdersEquity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_a0cc4973-bb04-4bbc-97a0-e531b27618c4" xlink:to="loc_us-gaap_StockholdersEquity_1dff760b-f41a-42f8-ac38-6ebaebbfcfc3" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_IssuanceOfStockFromVestedRestrictedStockUnitsAndPaymentOfEmployeesTaxesShares_e5e32caa-b42a-4663-b7e0-5316799132e7" xlink:href="exdx-20250331.xsd#exdx_IssuanceOfStockFromVestedRestrictedStockUnitsAndPaymentOfEmployeesTaxesShares"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_a0cc4973-bb04-4bbc-97a0-e531b27618c4" xlink:to="loc_exdx_IssuanceOfStockFromVestedRestrictedStockUnitsAndPaymentOfEmployeesTaxesShares_e5e32caa-b42a-4663-b7e0-5316799132e7" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans_e3c3185f-dd23-48d4-a28a-37089eb58247" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_a0cc4973-bb04-4bbc-97a0-e531b27618c4" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans_e3c3185f-dd23-48d4-a28a-37089eb58247" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueEmployeeStockPurchasePlan_b7a0298a-e1b7-4a63-a18c-1645be9ddca4" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockIssuedDuringPeriodValueEmployeeStockPurchasePlan"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_a0cc4973-bb04-4bbc-97a0-e531b27618c4" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueEmployeeStockPurchasePlan_b7a0298a-e1b7-4a63-a18c-1645be9ddca4" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_0120c8ff-792a-4fc8-8e8a-012083560a10" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_a0cc4973-bb04-4bbc-97a0-e531b27618c4" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_0120c8ff-792a-4fc8-8e8a-012083560a10" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_1bccf610-b6eb-4bee-bc0b-7162d767b235" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_a0cc4973-bb04-4bbc-97a0-e531b27618c4" xlink:to="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_1bccf610-b6eb-4bee-bc0b-7162d767b235" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_cbb8fb41-5937-4e17-b628-7ddce09ff8c8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_a0cc4973-bb04-4bbc-97a0-e531b27618c4" xlink:to="loc_us-gaap_NetIncomeLoss_cbb8fb41-5937-4e17-b628-7ddce09ff8c8" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockSharesOutstanding_100f5280-3ab2-43fa-a61c-392c697079a8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CommonStockSharesOutstanding"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_84740d55-0ce2-4f0e-94e4-ed8ecf8f9b56" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockholdersEquity"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.exagen.com/role/OrganizationDetails" xlink:type="simple" xlink:href="exdx-20250331.xsd#OrganizationDetails"/>
  <link:definitionLink xlink:role="http://www.exagen.com/role/OrganizationDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentLineItems_dcf25c54-8868-4388-be9d-4d336620050b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentTable_62bf731b-9315-4b6f-bad0-fe74e8fcf362" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DebtInstrumentLineItems_dcf25c54-8868-4388-be9d-4d336620050b" xlink:to="loc_us-gaap_DebtInstrumentTable_62bf731b-9315-4b6f-bad0-fe74e8fcf362" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityAxis_8f1473f6-c3ad-4219-abb3-444d22ed624a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CreditFacilityAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_62bf731b-9315-4b6f-bad0-fe74e8fcf362" xlink:to="loc_us-gaap_CreditFacilityAxis_8f1473f6-c3ad-4219-abb3-444d22ed624a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityDomain_8f1473f6-c3ad-4219-abb3-444d22ed624a_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CreditFacilityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_CreditFacilityAxis_8f1473f6-c3ad-4219-abb3-444d22ed624a" xlink:to="loc_us-gaap_CreditFacilityDomain_8f1473f6-c3ad-4219-abb3-444d22ed624a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityDomain_7a571d4c-75c4-4859-921d-a8f4d0b8dcca" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CreditFacilityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_CreditFacilityAxis_8f1473f6-c3ad-4219-abb3-444d22ed624a" xlink:to="loc_us-gaap_CreditFacilityDomain_7a571d4c-75c4-4859-921d-a8f4d0b8dcca" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DelayedDrawTermLoanMember_9b1f83f0-ff36-4b60-8455-018bf12e0338" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DelayedDrawTermLoanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CreditFacilityDomain_7a571d4c-75c4-4859-921d-a8f4d0b8dcca" xlink:to="loc_us-gaap_DelayedDrawTermLoanMember_9b1f83f0-ff36-4b60-8455-018bf12e0338" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentAxis_9575dd3f-02c4-4624-a346-8c436517d9d2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_62bf731b-9315-4b6f-bad0-fe74e8fcf362" xlink:to="loc_us-gaap_DebtInstrumentAxis_9575dd3f-02c4-4624-a346-8c436517d9d2" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_9575dd3f-02c4-4624-a346-8c436517d9d2_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DebtInstrumentAxis_9575dd3f-02c4-4624-a346-8c436517d9d2" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_9575dd3f-02c4-4624-a346-8c436517d9d2_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_c7ea86c6-a850-410c-8c21-042bac380a73" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DebtInstrumentAxis_9575dd3f-02c4-4624-a346-8c436517d9d2" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_c7ea86c6-a850-410c-8c21-042bac380a73" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_PerceptiveTermLoanFacilityTrancheALoanMember_c4e8f74c-2947-47ab-8a22-b8a526398cda" xlink:href="exdx-20250331.xsd#exdx_PerceptiveTermLoanFacilityTrancheALoanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_c7ea86c6-a850-410c-8c21-042bac380a73" xlink:to="loc_exdx_PerceptiveTermLoanFacilityTrancheALoanMember_c4e8f74c-2947-47ab-8a22-b8a526398cda" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_AmendedLoanAgreementMember_d2a351c2-3c9f-43b2-ba58-dd22c208f190" xlink:href="exdx-20250331.xsd#exdx_AmendedLoanAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_c7ea86c6-a850-410c-8c21-042bac380a73" xlink:to="loc_exdx_AmendedLoanAgreementMember_d2a351c2-3c9f-43b2-ba58-dd22c208f190" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityAxis_3a0865cf-2262-4c50-8664-218b953f10a5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LineOfCreditFacilityAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_62bf731b-9315-4b6f-bad0-fe74e8fcf362" xlink:to="loc_us-gaap_LineOfCreditFacilityAxis_3a0865cf-2262-4c50-8664-218b953f10a5" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityLenderDomain_3a0865cf-2262-4c50-8664-218b953f10a5_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LineOfCreditFacilityLenderDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_LineOfCreditFacilityAxis_3a0865cf-2262-4c50-8664-218b953f10a5" xlink:to="loc_us-gaap_LineOfCreditFacilityLenderDomain_3a0865cf-2262-4c50-8664-218b953f10a5_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityLenderDomain_18fa955c-cb9c-44f1-bc19-78c85e8237b5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LineOfCreditFacilityLenderDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_LineOfCreditFacilityAxis_3a0865cf-2262-4c50-8664-218b953f10a5" xlink:to="loc_us-gaap_LineOfCreditFacilityLenderDomain_18fa955c-cb9c-44f1-bc19-78c85e8237b5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_PerceptiveCreditHoldingsIVLPMember_3f88ec57-7785-4f12-aed7-8121678a64df" xlink:href="exdx-20250331.xsd#exdx_PerceptiveCreditHoldingsIVLPMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLenderDomain_18fa955c-cb9c-44f1-bc19-78c85e8237b5" xlink:to="loc_exdx_PerceptiveCreditHoldingsIVLPMember_3f88ec57-7785-4f12-aed7-8121678a64df" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_InnovatusLifeSciencesLendingFundMember_5ab9225a-73d8-4b20-81c1-841284c1bc43" xlink:href="exdx-20250331.xsd#exdx_InnovatusLifeSciencesLendingFundMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLenderDomain_18fa955c-cb9c-44f1-bc19-78c85e8237b5" xlink:to="loc_exdx_InnovatusLifeSciencesLendingFundMember_5ab9225a-73d8-4b20-81c1-841284c1bc43" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeAxis_e265bb4c-2b51-43d7-8202-89d06394f1fa" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongtermDebtTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_62bf731b-9315-4b6f-bad0-fe74e8fcf362" xlink:to="loc_us-gaap_LongtermDebtTypeAxis_e265bb4c-2b51-43d7-8202-89d06394f1fa" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_e265bb4c-2b51-43d7-8202-89d06394f1fa_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongtermDebtTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_e265bb4c-2b51-43d7-8202-89d06394f1fa" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_e265bb4c-2b51-43d7-8202-89d06394f1fa_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_9a2bf85a-84ca-48ec-854f-5c7b7364f038" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongtermDebtTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_e265bb4c-2b51-43d7-8202-89d06394f1fa" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_9a2bf85a-84ca-48ec-854f-5c7b7364f038" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LoansPayableMember_e67b8a34-ecc9-41db-aa12-b705f1fae821" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LoansPayableMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongtermDebtTypeDomain_9a2bf85a-84ca-48ec-854f-5c7b7364f038" xlink:to="loc_us-gaap_LoansPayableMember_e67b8a34-ecc9-41db-aa12-b705f1fae821" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeAxis_936c9f46-c1ff-467a-a501-9b2a8570d820" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SubsequentEventTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_62bf731b-9315-4b6f-bad0-fe74e8fcf362" xlink:to="loc_us-gaap_SubsequentEventTypeAxis_936c9f46-c1ff-467a-a501-9b2a8570d820" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeDomain_936c9f46-c1ff-467a-a501-9b2a8570d820_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SubsequentEventTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_SubsequentEventTypeAxis_936c9f46-c1ff-467a-a501-9b2a8570d820" xlink:to="loc_us-gaap_SubsequentEventTypeDomain_936c9f46-c1ff-467a-a501-9b2a8570d820_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeDomain_2aa3fdc3-1b10-48bd-aa51-8b97e58e0e2f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SubsequentEventTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_SubsequentEventTypeAxis_936c9f46-c1ff-467a-a501-9b2a8570d820" xlink:to="loc_us-gaap_SubsequentEventTypeDomain_2aa3fdc3-1b10-48bd-aa51-8b97e58e0e2f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventMember_a80c99c7-989e-469f-bb6b-09db66ef53a4" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SubsequentEventMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventTypeDomain_2aa3fdc3-1b10-48bd-aa51-8b97e58e0e2f" xlink:to="loc_us-gaap_SubsequentEventMember_a80c99c7-989e-469f-bb6b-09db66ef53a4" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_7a563ea3-8875-4cda-ad50-03d0d76ee590" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_dcf25c54-8868-4388-be9d-4d336620050b" xlink:to="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_7a563ea3-8875-4cda-ad50-03d0d76ee590" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetainedEarningsAccumulatedDeficit_7a51ce66-a0c0-49f4-906e-1f8ae9bc5722" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RetainedEarningsAccumulatedDeficit"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_dcf25c54-8868-4388-be9d-4d336620050b" xlink:to="loc_us-gaap_RetainedEarningsAccumulatedDeficit_7a51ce66-a0c0-49f4-906e-1f8ae9bc5722" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromLongTermLinesOfCredit_ad9931c6-322a-4f40-8efd-a28f4f461664" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ProceedsFromLongTermLinesOfCredit"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_dcf25c54-8868-4388-be9d-4d336620050b" xlink:to="loc_us-gaap_ProceedsFromLongTermLinesOfCredit_ad9931c6-322a-4f40-8efd-a28f4f461664" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RepaymentsOfLongTermDebt_53537145-8cee-4bae-9256-f6a19489721f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RepaymentsOfLongTermDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_dcf25c54-8868-4388-be9d-4d336620050b" xlink:to="loc_us-gaap_RepaymentsOfLongTermDebt_53537145-8cee-4bae-9256-f6a19489721f" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.exagen.com/role/SummaryofSignificantAccountingPoliciesRevenuebyMajorPayersDetails" xlink:type="simple" xlink:href="exdx-20250331.xsd#SummaryofSignificantAccountingPoliciesRevenuebyMajorPayersDetails"/>
  <link:definitionLink xlink:role="http://www.exagen.com/role/SummaryofSignificantAccountingPoliciesRevenuebyMajorPayersDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueLineItems_eb45e55c-0e37-4f2a-a575-7f2d5cbe50ec" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DisaggregationOfRevenueLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueTable_766f6b0a-a00e-4847-94d3-cd5ef6800365" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DisaggregationOfRevenueTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_eb45e55c-0e37-4f2a-a575-7f2d5cbe50ec" xlink:to="loc_us-gaap_DisaggregationOfRevenueTable_766f6b0a-a00e-4847-94d3-cd5ef6800365" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MajorCustomersAxis_fba5ab6e-ce2b-455a-9098-004c5867d418" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_MajorCustomersAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DisaggregationOfRevenueTable_766f6b0a-a00e-4847-94d3-cd5ef6800365" xlink:to="loc_srt_MajorCustomersAxis_fba5ab6e-ce2b-455a-9098-004c5867d418" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_NameOfMajorCustomerDomain_fba5ab6e-ce2b-455a-9098-004c5867d418_default" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_NameOfMajorCustomerDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_MajorCustomersAxis_fba5ab6e-ce2b-455a-9098-004c5867d418" xlink:to="loc_srt_NameOfMajorCustomerDomain_fba5ab6e-ce2b-455a-9098-004c5867d418_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_NameOfMajorCustomerDomain_fc2e8613-d957-4799-b59a-b9f0ecd09d9d" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_NameOfMajorCustomerDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_MajorCustomersAxis_fba5ab6e-ce2b-455a-9098-004c5867d418" xlink:to="loc_srt_NameOfMajorCustomerDomain_fc2e8613-d957-4799-b59a-b9f0ecd09d9d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_MedicareMember_35dc9541-3834-4dbb-bebf-a864f9b05661" xlink:href="exdx-20250331.xsd#exdx_MedicareMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_NameOfMajorCustomerDomain_fc2e8613-d957-4799-b59a-b9f0ecd09d9d" xlink:to="loc_exdx_MedicareMember_35dc9541-3834-4dbb-bebf-a864f9b05661" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_MedicareAdvantageMember_5c83e2ee-ff34-472a-b27f-62a531836bd1" xlink:href="exdx-20250331.xsd#exdx_MedicareAdvantageMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_NameOfMajorCustomerDomain_fc2e8613-d957-4799-b59a-b9f0ecd09d9d" xlink:to="loc_exdx_MedicareAdvantageMember_5c83e2ee-ff34-472a-b27f-62a531836bd1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_UnitedHealthcareMember_bc202d2c-2887-48df-8095-263120d9f231" xlink:href="exdx-20250331.xsd#exdx_UnitedHealthcareMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_NameOfMajorCustomerDomain_fc2e8613-d957-4799-b59a-b9f0ecd09d9d" xlink:to="loc_exdx_UnitedHealthcareMember_bc202d2c-2887-48df-8095-263120d9f231" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_9b9939a2-c634-4af1-9e6a-a40c15a55cba" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConcentrationRiskByBenchmarkAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DisaggregationOfRevenueTable_766f6b0a-a00e-4847-94d3-cd5ef6800365" xlink:to="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_9b9939a2-c634-4af1-9e6a-a40c15a55cba" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskBenchmarkDomain_9b9939a2-c634-4af1-9e6a-a40c15a55cba_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConcentrationRiskBenchmarkDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_9b9939a2-c634-4af1-9e6a-a40c15a55cba" xlink:to="loc_us-gaap_ConcentrationRiskBenchmarkDomain_9b9939a2-c634-4af1-9e6a-a40c15a55cba_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskBenchmarkDomain_9b1ca00b-bcb7-426d-8143-26e50049609c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConcentrationRiskBenchmarkDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_9b9939a2-c634-4af1-9e6a-a40c15a55cba" xlink:to="loc_us-gaap_ConcentrationRiskBenchmarkDomain_9b1ca00b-bcb7-426d-8143-26e50049609c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SalesRevenueNetMember_c341b1b4-a5f6-46b0-ba0a-00b1924b75cf" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SalesRevenueNetMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskBenchmarkDomain_9b1ca00b-bcb7-426d-8143-26e50049609c" xlink:to="loc_us-gaap_SalesRevenueNetMember_c341b1b4-a5f6-46b0-ba0a-00b1924b75cf" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsReceivableMember_210d7aef-dfa3-467d-abc2-fac7552cd7b4" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AccountsReceivableMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskBenchmarkDomain_9b1ca00b-bcb7-426d-8143-26e50049609c" xlink:to="loc_us-gaap_AccountsReceivableMember_210d7aef-dfa3-467d-abc2-fac7552cd7b4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskByTypeAxis_19eceb7f-ce49-42e4-b315-740c26f6efdb" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConcentrationRiskByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DisaggregationOfRevenueTable_766f6b0a-a00e-4847-94d3-cd5ef6800365" xlink:to="loc_us-gaap_ConcentrationRiskByTypeAxis_19eceb7f-ce49-42e4-b315-740c26f6efdb" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskTypeDomain_19eceb7f-ce49-42e4-b315-740c26f6efdb_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConcentrationRiskTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ConcentrationRiskByTypeAxis_19eceb7f-ce49-42e4-b315-740c26f6efdb" xlink:to="loc_us-gaap_ConcentrationRiskTypeDomain_19eceb7f-ce49-42e4-b315-740c26f6efdb_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskTypeDomain_21b89030-6a59-4107-a4ac-2503bd7d7954" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConcentrationRiskTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ConcentrationRiskByTypeAxis_19eceb7f-ce49-42e4-b315-740c26f6efdb" xlink:to="loc_us-gaap_ConcentrationRiskTypeDomain_21b89030-6a59-4107-a4ac-2503bd7d7954" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CustomerConcentrationRiskMember_a2f60fa4-4c90-448e-85b2-1e5bcf4c10b5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CustomerConcentrationRiskMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskTypeDomain_21b89030-6a59-4107-a4ac-2503bd7d7954" xlink:to="loc_us-gaap_CustomerConcentrationRiskMember_a2f60fa4-4c90-448e-85b2-1e5bcf4c10b5" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskPercentage1_05a882f8-1071-48fe-9c9e-80b02ef4afb5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConcentrationRiskPercentage1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_eb45e55c-0e37-4f2a-a575-7f2d5cbe50ec" xlink:to="loc_us-gaap_ConcentrationRiskPercentage1_05a882f8-1071-48fe-9c9e-80b02ef4afb5" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.exagen.com/role/SummaryofSignificantAccountingPoliciesNarrativeDetails" xlink:type="simple" xlink:href="exdx-20250331.xsd#SummaryofSignificantAccountingPoliciesNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.exagen.com/role/SummaryofSignificantAccountingPoliciesNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems_bfec250a-4497-4abf-87e6-7c8903a855e1" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable_c42d2eac-45a1-48ba-a792-fba6f5b3891f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems_bfec250a-4497-4abf-87e6-7c8903a855e1" xlink:to="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable_c42d2eac-45a1-48ba-a792-fba6f5b3891f" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_87dc027c-a395-4dea-9866-987d2c8038ee" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConcentrationRiskByBenchmarkAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable_c42d2eac-45a1-48ba-a792-fba6f5b3891f" xlink:to="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_87dc027c-a395-4dea-9866-987d2c8038ee" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskBenchmarkDomain_87dc027c-a395-4dea-9866-987d2c8038ee_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConcentrationRiskBenchmarkDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_87dc027c-a395-4dea-9866-987d2c8038ee" xlink:to="loc_us-gaap_ConcentrationRiskBenchmarkDomain_87dc027c-a395-4dea-9866-987d2c8038ee_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskBenchmarkDomain_5630c668-8399-414e-b1e6-d325029110b0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConcentrationRiskBenchmarkDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_87dc027c-a395-4dea-9866-987d2c8038ee" xlink:to="loc_us-gaap_ConcentrationRiskBenchmarkDomain_5630c668-8399-414e-b1e6-d325029110b0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SalesRevenueNetMember_cb7a358c-1f03-4270-833e-0a6b00da10b8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SalesRevenueNetMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskBenchmarkDomain_5630c668-8399-414e-b1e6-d325029110b0" xlink:to="loc_us-gaap_SalesRevenueNetMember_cb7a358c-1f03-4270-833e-0a6b00da10b8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskByTypeAxis_f3bb8f4d-dc70-478d-9ca3-f0356a199057" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConcentrationRiskByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable_c42d2eac-45a1-48ba-a792-fba6f5b3891f" xlink:to="loc_us-gaap_ConcentrationRiskByTypeAxis_f3bb8f4d-dc70-478d-9ca3-f0356a199057" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskTypeDomain_f3bb8f4d-dc70-478d-9ca3-f0356a199057_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConcentrationRiskTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ConcentrationRiskByTypeAxis_f3bb8f4d-dc70-478d-9ca3-f0356a199057" xlink:to="loc_us-gaap_ConcentrationRiskTypeDomain_f3bb8f4d-dc70-478d-9ca3-f0356a199057_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskTypeDomain_ebaebee6-9b5a-4c58-9aa5-0aa76dee1545" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConcentrationRiskTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ConcentrationRiskByTypeAxis_f3bb8f4d-dc70-478d-9ca3-f0356a199057" xlink:to="loc_us-gaap_ConcentrationRiskTypeDomain_ebaebee6-9b5a-4c58-9aa5-0aa76dee1545" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProductConcentrationRiskMember_dd5ddc25-9dad-4f45-ae4c-2e9f41e4b0b5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ProductConcentrationRiskMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskTypeDomain_ebaebee6-9b5a-4c58-9aa5-0aa76dee1545" xlink:to="loc_us-gaap_ProductConcentrationRiskMember_dd5ddc25-9dad-4f45-ae4c-2e9f41e4b0b5" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SupplierConcentrationRiskMember_3ec46d41-e04f-4c4e-9c99-e77caf7c7488" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SupplierConcentrationRiskMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskTypeDomain_ebaebee6-9b5a-4c58-9aa5-0aa76dee1545" xlink:to="loc_us-gaap_SupplierConcentrationRiskMember_3ec46d41-e04f-4c4e-9c99-e77caf7c7488" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_80909114-aaac-49c2-bfdd-f0c44697d186" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable_c42d2eac-45a1-48ba-a792-fba6f5b3891f" xlink:to="loc_srt_ProductOrServiceAxis_80909114-aaac-49c2-bfdd-f0c44697d186" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_80909114-aaac-49c2-bfdd-f0c44697d186_default" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_80909114-aaac-49c2-bfdd-f0c44697d186" xlink:to="loc_srt_ProductsAndServicesDomain_80909114-aaac-49c2-bfdd-f0c44697d186_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_d4b76c1c-956f-494d-9509-9d65e5a99bce" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_80909114-aaac-49c2-bfdd-f0c44697d186" xlink:to="loc_srt_ProductsAndServicesDomain_d4b76c1c-956f-494d-9509-9d65e5a99bce" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_AVISECTDTestMember_b35f8456-1cec-48e3-8d15-953fe3d40d01" xlink:href="exdx-20250331.xsd#exdx_AVISECTDTestMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_d4b76c1c-956f-494d-9509-9d65e5a99bce" xlink:to="loc_exdx_AVISECTDTestMember_b35f8456-1cec-48e3-8d15-953fe3d40d01" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedGoodsAndNonemployeeServicesTransactionBySupplierAxis_fd77a0fe-a2d7-497c-b376-7db1a5154c7e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedGoodsAndNonemployeeServicesTransactionBySupplierAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable_c42d2eac-45a1-48ba-a792-fba6f5b3891f" xlink:to="loc_us-gaap_ShareBasedGoodsAndNonemployeeServicesTransactionBySupplierAxis_fd77a0fe-a2d7-497c-b376-7db1a5154c7e" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedGoodsAndNonemployeeServicesTransactionSupplierDomain_fd77a0fe-a2d7-497c-b376-7db1a5154c7e_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedGoodsAndNonemployeeServicesTransactionSupplierDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ShareBasedGoodsAndNonemployeeServicesTransactionBySupplierAxis_fd77a0fe-a2d7-497c-b376-7db1a5154c7e" xlink:to="loc_us-gaap_ShareBasedGoodsAndNonemployeeServicesTransactionSupplierDomain_fd77a0fe-a2d7-497c-b376-7db1a5154c7e_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedGoodsAndNonemployeeServicesTransactionSupplierDomain_827a160b-0fa6-47ef-890b-a6ea52dfb001" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedGoodsAndNonemployeeServicesTransactionSupplierDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ShareBasedGoodsAndNonemployeeServicesTransactionBySupplierAxis_fd77a0fe-a2d7-497c-b376-7db1a5154c7e" xlink:to="loc_us-gaap_ShareBasedGoodsAndNonemployeeServicesTransactionSupplierDomain_827a160b-0fa6-47ef-890b-a6ea52dfb001" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_TwoSuppliersMember_9cde052b-75b6-4f65-aef0-e073c0b7130e" xlink:href="exdx-20250331.xsd#exdx_TwoSuppliersMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedGoodsAndNonemployeeServicesTransactionSupplierDomain_827a160b-0fa6-47ef-890b-a6ea52dfb001" xlink:to="loc_exdx_TwoSuppliersMember_9cde052b-75b6-4f65-aef0-e073c0b7130e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskPercentage1_1b0b9e8e-3d69-4de7-9842-4a5a814f2c7e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConcentrationRiskPercentage1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems_bfec250a-4497-4abf-87e6-7c8903a855e1" xlink:to="loc_us-gaap_ConcentrationRiskPercentage1_1b0b9e8e-3d69-4de7-9842-4a5a814f2c7e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCash_89810bbb-7a21-45ab-86cf-3c9bf76e1f6e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RestrictedCash"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems_bfec250a-4497-4abf-87e6-7c8903a855e1" xlink:to="loc_us-gaap_RestrictedCash_89810bbb-7a21-45ab-86cf-3c9bf76e1f6e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityChangeInTimeframePerformanceObligationSatisfiedRevenueRecognized_05401fa4-ca93-42d5-8b95-d49e8e8483b3" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ContractWithCustomerLiabilityChangeInTimeframePerformanceObligationSatisfiedRevenueRecognized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems_bfec250a-4497-4abf-87e6-7c8903a855e1" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityChangeInTimeframePerformanceObligationSatisfiedRevenueRecognized_05401fa4-ca93-42d5-8b95-d49e8e8483b3" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiability_6091478e-e1a2-4300-abf9-d75323a7ccb9" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ContractWithCustomerLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems_bfec250a-4497-4abf-87e6-7c8903a855e1" xlink:to="loc_us-gaap_ContractWithCustomerLiability_6091478e-e1a2-4300-abf9-d75323a7ccb9" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityRevenueRecognized_fff5bd34-a3db-4392-9248-b8ff2da04432" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ContractWithCustomerLiabilityRevenueRecognized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems_bfec250a-4497-4abf-87e6-7c8903a855e1" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityRevenueRecognized_fff5bd34-a3db-4392-9248-b8ff2da04432" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancingReceivableAllowanceForCreditLossExcludingAccruedInterest_c0b72a45-4d13-4388-96b6-37e0403be25c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FinancingReceivableAllowanceForCreditLossExcludingAccruedInterest"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems_bfec250a-4497-4abf-87e6-7c8903a855e1" xlink:to="loc_us-gaap_FinancingReceivableAllowanceForCreditLossExcludingAccruedInterest_c0b72a45-4d13-4388-96b6-37e0403be25c" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsReceivableNetCurrent_61f47b0f-207a-4761-80a6-853ee55fc03f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AccountsReceivableNetCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems_bfec250a-4497-4abf-87e6-7c8903a855e1" xlink:to="loc_us-gaap_AccountsReceivableNetCurrent_61f47b0f-207a-4761-80a6-853ee55fc03f" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAnnualInstallments_832cfd55-50c8-468c-980d-564b46a98924" xlink:href="exdx-20250331.xsd#exdx_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAnnualInstallments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems_bfec250a-4497-4abf-87e6-7c8903a855e1" xlink:to="loc_exdx_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAnnualInstallments_832cfd55-50c8-468c-980d-564b46a98924" xlink:type="arc" order="7"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.exagen.com/role/SummaryofSignificantAccountingPoliciesDisaggregationofRevenueDetails" xlink:type="simple" xlink:href="exdx-20250331.xsd#SummaryofSignificantAccountingPoliciesDisaggregationofRevenueDetails"/>
  <link:definitionLink xlink:role="http://www.exagen.com/role/SummaryofSignificantAccountingPoliciesDisaggregationofRevenueDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueLineItems_6567e516-233a-4c05-b556-3c0132a8234d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DisaggregationOfRevenueLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueTable_b87a677e-e50e-44ef-b51d-ba2673762300" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DisaggregationOfRevenueTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_6567e516-233a-4c05-b556-3c0132a8234d" xlink:to="loc_us-gaap_DisaggregationOfRevenueTable_b87a677e-e50e-44ef-b51d-ba2673762300" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MajorCustomersAxis_db191bd7-e36f-45e5-8667-187997add504" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_MajorCustomersAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DisaggregationOfRevenueTable_b87a677e-e50e-44ef-b51d-ba2673762300" xlink:to="loc_srt_MajorCustomersAxis_db191bd7-e36f-45e5-8667-187997add504" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_NameOfMajorCustomerDomain_db191bd7-e36f-45e5-8667-187997add504_default" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_NameOfMajorCustomerDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_MajorCustomersAxis_db191bd7-e36f-45e5-8667-187997add504" xlink:to="loc_srt_NameOfMajorCustomerDomain_db191bd7-e36f-45e5-8667-187997add504_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_NameOfMajorCustomerDomain_37195a43-f035-4dab-aa34-3bb1c0b2886d" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_NameOfMajorCustomerDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_MajorCustomersAxis_db191bd7-e36f-45e5-8667-187997add504" xlink:to="loc_srt_NameOfMajorCustomerDomain_37195a43-f035-4dab-aa34-3bb1c0b2886d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_CommercialMember_c96642fd-3207-4cbb-a816-7c8f6ae5c0f4" xlink:href="exdx-20250331.xsd#exdx_CommercialMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_NameOfMajorCustomerDomain_37195a43-f035-4dab-aa34-3bb1c0b2886d" xlink:to="loc_exdx_CommercialMember_c96642fd-3207-4cbb-a816-7c8f6ae5c0f4" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_Government1Member_e52a8da4-ceae-42e3-9c9b-3b1921525a5e" xlink:href="exdx-20250331.xsd#exdx_Government1Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_NameOfMajorCustomerDomain_37195a43-f035-4dab-aa34-3bb1c0b2886d" xlink:to="loc_exdx_Government1Member_e52a8da4-ceae-42e3-9c9b-3b1921525a5e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_ClientDirectBillMember_0e44c661-434a-412a-9a93-9412abc9af1e" xlink:href="exdx-20250331.xsd#exdx_ClientDirectBillMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_NameOfMajorCustomerDomain_37195a43-f035-4dab-aa34-3bb1c0b2886d" xlink:to="loc_exdx_ClientDirectBillMember_0e44c661-434a-412a-9a93-9412abc9af1e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherCustomerMember_97b66315-9ac4-4bbb-baa1-aa495d5e3827" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherCustomerMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_NameOfMajorCustomerDomain_37195a43-f035-4dab-aa34-3bb1c0b2886d" xlink:to="loc_us-gaap_OtherCustomerMember_97b66315-9ac4-4bbb-baa1-aa495d5e3827" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_c50396b8-d421-4267-8e37-876ffcfe504a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_6567e516-233a-4c05-b556-3c0132a8234d" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_c50396b8-d421-4267-8e37-876ffcfe504a" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.exagen.com/role/SummaryofSignificantAccountingPoliciesSecuritiesDetails" xlink:type="simple" xlink:href="exdx-20250331.xsd#SummaryofSignificantAccountingPoliciesSecuritiesDetails"/>
  <link:definitionLink xlink:role="http://www.exagen.com/role/SummaryofSignificantAccountingPoliciesSecuritiesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockLineItems_d59a249a-5aed-45b1-80dd-0820b51e94f4" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ClassOfStockLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfStockByClassTable_e9f53723-5d46-4abe-aaf4-c0218b12dc94" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfStockByClassTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ClassOfStockLineItems_d59a249a-5aed-45b1-80dd-0820b51e94f4" xlink:to="loc_us-gaap_ScheduleOfStockByClassTable_e9f53723-5d46-4abe-aaf4-c0218b12dc94" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_00dd325c-d4f8-466b-aee4-bc02151fe7ef" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfStockByClassTable_e9f53723-5d46-4abe-aaf4-c0218b12dc94" xlink:to="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_00dd325c-d4f8-466b-aee4-bc02151fe7ef" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesNameDomain_00dd325c-d4f8-466b-aee4-bc02151fe7ef_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AntidilutiveSecuritiesNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_00dd325c-d4f8-466b-aee4-bc02151fe7ef" xlink:to="loc_us-gaap_AntidilutiveSecuritiesNameDomain_00dd325c-d4f8-466b-aee4-bc02151fe7ef_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesNameDomain_c81a516c-5567-489e-9ae6-e4af3eea056c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AntidilutiveSecuritiesNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_00dd325c-d4f8-466b-aee4-bc02151fe7ef" xlink:to="loc_us-gaap_AntidilutiveSecuritiesNameDomain_c81a516c-5567-489e-9ae6-e4af3eea056c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WarrantMember_9be1e208-7280-4d25-a438-7a121ecaeac5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_WarrantMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_c81a516c-5567-489e-9ae6-e4af3eea056c" xlink:to="loc_us-gaap_WarrantMember_9be1e208-7280-4d25-a438-7a121ecaeac5" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockOptionMember_eb1b0847-3752-48d7-a04c-78efe59e47db" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_c81a516c-5567-489e-9ae6-e4af3eea056c" xlink:to="loc_us-gaap_StockOptionMember_eb1b0847-3752-48d7-a04c-78efe59e47db" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_f5c22cc9-2b64-45b1-b236-e4ba29e09f70" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_c81a516c-5567-489e-9ae6-e4af3eea056c" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_f5c22cc9-2b64-45b1-b236-e4ba29e09f70" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockMember_b2b27a3a-acc7-4b5b-9891-4982806c1a18" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EmployeeStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_c81a516c-5567-489e-9ae6-e4af3eea056c" xlink:to="loc_us-gaap_EmployeeStockMember_b2b27a3a-acc7-4b5b-9891-4982806c1a18" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount_86435926-bceb-4666-96f5-2720b1614a25" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_d59a249a-5aed-45b1-80dd-0820b51e94f4" xlink:to="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount_86435926-bceb-4666-96f5-2720b1614a25" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.exagen.com/role/OtherFinancialInformationPropertyandEquipmentnetDetails" xlink:type="simple" xlink:href="exdx-20250331.xsd#OtherFinancialInformationPropertyandEquipmentnetDetails"/>
  <link:definitionLink xlink:role="http://www.exagen.com/role/OtherFinancialInformationPropertyandEquipmentnetDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentLineItems_52508d19-685d-4fa4-9532-3f7d984dfb8f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PropertyPlantAndEquipmentLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_4554330e-8b99-4eba-932e-54207eb1a4ab" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfPropertyPlantAndEquipmentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_52508d19-685d-4fa4-9532-3f7d984dfb8f" xlink:to="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_4554330e-8b99-4eba-932e-54207eb1a4ab" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_c46002e8-0a05-4062-8721-299813017228" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PropertyPlantAndEquipmentByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_4554330e-8b99-4eba-932e-54207eb1a4ab" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_c46002e8-0a05-4062-8721-299813017228" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_c46002e8-0a05-4062-8721-299813017228_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_c46002e8-0a05-4062-8721-299813017228" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_c46002e8-0a05-4062-8721-299813017228_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_371664cc-0682-44b5-bb52-7a7bb1b15ffc" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_c46002e8-0a05-4062-8721-299813017228" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_371664cc-0682-44b5-bb52-7a7bb1b15ffc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FurnitureAndFixturesMember_2b47d04c-78c3-49c2-9ba3-51601ea60534" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FurnitureAndFixturesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_371664cc-0682-44b5-bb52-7a7bb1b15ffc" xlink:to="loc_us-gaap_FurnitureAndFixturesMember_2b47d04c-78c3-49c2-9ba3-51601ea60534" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_LaboratoryEquipmentMember_d541ced6-5de4-460e-9d7f-9ef83e06c2b9" xlink:href="exdx-20250331.xsd#exdx_LaboratoryEquipmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_371664cc-0682-44b5-bb52-7a7bb1b15ffc" xlink:to="loc_exdx_LaboratoryEquipmentMember_d541ced6-5de4-460e-9d7f-9ef83e06c2b9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_ComputerEquipmentAndSoftwareMember_35d5f0a6-fcc9-47d2-8d6f-7bcb6a6c75c7" xlink:href="exdx-20250331.xsd#exdx_ComputerEquipmentAndSoftwareMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_371664cc-0682-44b5-bb52-7a7bb1b15ffc" xlink:to="loc_exdx_ComputerEquipmentAndSoftwareMember_35d5f0a6-fcc9-47d2-8d6f-7bcb6a6c75c7" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LeaseholdImprovementsMember_cd32d078-140e-44a4-b5fe-f477a44a1e30" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LeaseholdImprovementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_371664cc-0682-44b5-bb52-7a7bb1b15ffc" xlink:to="loc_us-gaap_LeaseholdImprovementsMember_cd32d078-140e-44a4-b5fe-f477a44a1e30" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConstructionInProgressMember_68e8542a-50e9-4cb3-9f07-950bd6096e39" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConstructionInProgressMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_371664cc-0682-44b5-bb52-7a7bb1b15ffc" xlink:to="loc_us-gaap_ConstructionInProgressMember_68e8542a-50e9-4cb3-9f07-950bd6096e39" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentAndFinanceLeaseRightOfUseAssetBeforeAccumulatedDepreciationAndAmortization_d98db560-179b-40b5-a38d-3b358b7d9523" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PropertyPlantAndEquipmentAndFinanceLeaseRightOfUseAssetBeforeAccumulatedDepreciationAndAmortization"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_52508d19-685d-4fa4-9532-3f7d984dfb8f" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentAndFinanceLeaseRightOfUseAssetBeforeAccumulatedDepreciationAndAmortization_d98db560-179b-40b5-a38d-3b358b7d9523" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentAndFinanceLeaseRightOfUseAssetAccumulatedDepreciationAndAmortization_6478c2af-6a6e-41b7-86a4-245c64dc13c1" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PropertyPlantAndEquipmentAndFinanceLeaseRightOfUseAssetAccumulatedDepreciationAndAmortization"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_52508d19-685d-4fa4-9532-3f7d984dfb8f" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentAndFinanceLeaseRightOfUseAssetAccumulatedDepreciationAndAmortization_6478c2af-6a6e-41b7-86a4-245c64dc13c1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentAndFinanceLeaseRightOfUseAssetAfterAccumulatedDepreciationAndAmortization_70e8d8cf-c8e9-4e50-b284-94778e9a25ca" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PropertyPlantAndEquipmentAndFinanceLeaseRightOfUseAssetAfterAccumulatedDepreciationAndAmortization"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_52508d19-685d-4fa4-9532-3f7d984dfb8f" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentAndFinanceLeaseRightOfUseAssetAfterAccumulatedDepreciationAndAmortization_70e8d8cf-c8e9-4e50-b284-94778e9a25ca" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.exagen.com/role/BorrowingsNarrativeDetails" xlink:type="simple" xlink:href="exdx-20250331.xsd#BorrowingsNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.exagen.com/role/BorrowingsNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentLineItems_eaf5e6f3-b0a1-4d3e-89e2-2b17be709828" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentTable_7fe99f7b-2a4c-41d0-ab86-381efd1c1e64" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DebtInstrumentLineItems_eaf5e6f3-b0a1-4d3e-89e2-2b17be709828" xlink:to="loc_us-gaap_DebtInstrumentTable_7fe99f7b-2a4c-41d0-ab86-381efd1c1e64" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentAxis_2f586af9-554b-41e3-8d75-c63561d65f1e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_7fe99f7b-2a4c-41d0-ab86-381efd1c1e64" xlink:to="loc_us-gaap_DebtInstrumentAxis_2f586af9-554b-41e3-8d75-c63561d65f1e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_2f586af9-554b-41e3-8d75-c63561d65f1e_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DebtInstrumentAxis_2f586af9-554b-41e3-8d75-c63561d65f1e" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_2f586af9-554b-41e3-8d75-c63561d65f1e_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_17c3d3a6-2a05-4239-bf24-3c1437361390" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DebtInstrumentAxis_2f586af9-554b-41e3-8d75-c63561d65f1e" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_17c3d3a6-2a05-4239-bf24-3c1437361390" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_AmendedLoanAgreementMember_84e37806-d3f1-4127-af41-e84b295c23d8" xlink:href="exdx-20250331.xsd#exdx_AmendedLoanAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_17c3d3a6-2a05-4239-bf24-3c1437361390" xlink:to="loc_exdx_AmendedLoanAgreementMember_84e37806-d3f1-4127-af41-e84b295c23d8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_Term2017Member_2bee9f07-b3dd-480c-8556-21662c5ffc85" xlink:href="exdx-20250331.xsd#exdx_Term2017Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_17c3d3a6-2a05-4239-bf24-3c1437361390" xlink:to="loc_exdx_Term2017Member_2bee9f07-b3dd-480c-8556-21662c5ffc85" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_PerceptiveTermLoanFacilityTrancheALoanMember_fbca82b4-d510-430b-a489-bce5db5f8785" xlink:href="exdx-20250331.xsd#exdx_PerceptiveTermLoanFacilityTrancheALoanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_17c3d3a6-2a05-4239-bf24-3c1437361390" xlink:to="loc_exdx_PerceptiveTermLoanFacilityTrancheALoanMember_fbca82b4-d510-430b-a489-bce5db5f8785" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_EquipmentNotesPayableMember_7aecd9bc-076f-411d-9e3e-860fe28a4677" xlink:href="exdx-20250331.xsd#exdx_EquipmentNotesPayableMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_17c3d3a6-2a05-4239-bf24-3c1437361390" xlink:to="loc_exdx_EquipmentNotesPayableMember_7aecd9bc-076f-411d-9e3e-860fe28a4677" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityAxis_04c6d9db-fe0c-4aae-bbba-0035933edad6" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LineOfCreditFacilityAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_7fe99f7b-2a4c-41d0-ab86-381efd1c1e64" xlink:to="loc_us-gaap_LineOfCreditFacilityAxis_04c6d9db-fe0c-4aae-bbba-0035933edad6" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityLenderDomain_04c6d9db-fe0c-4aae-bbba-0035933edad6_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LineOfCreditFacilityLenderDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_LineOfCreditFacilityAxis_04c6d9db-fe0c-4aae-bbba-0035933edad6" xlink:to="loc_us-gaap_LineOfCreditFacilityLenderDomain_04c6d9db-fe0c-4aae-bbba-0035933edad6_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityLenderDomain_21693df0-1018-40e9-9054-67c639215cc7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LineOfCreditFacilityLenderDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_LineOfCreditFacilityAxis_04c6d9db-fe0c-4aae-bbba-0035933edad6" xlink:to="loc_us-gaap_LineOfCreditFacilityLenderDomain_21693df0-1018-40e9-9054-67c639215cc7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_InnovatusLifeSciencesLendingFundMember_60d640c8-dd46-46b7-977c-1548ed423440" xlink:href="exdx-20250331.xsd#exdx_InnovatusLifeSciencesLendingFundMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLenderDomain_21693df0-1018-40e9-9054-67c639215cc7" xlink:to="loc_exdx_InnovatusLifeSciencesLendingFundMember_60d640c8-dd46-46b7-977c-1548ed423440" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_PerceptiveCreditHoldingsIVLPMember_20c94d15-f598-428c-ac94-4c0e6f224747" xlink:href="exdx-20250331.xsd#exdx_PerceptiveCreditHoldingsIVLPMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLenderDomain_21693df0-1018-40e9-9054-67c639215cc7" xlink:to="loc_exdx_PerceptiveCreditHoldingsIVLPMember_20c94d15-f598-428c-ac94-4c0e6f224747" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeAxis_bc13abf2-df06-4bf7-ac3a-65f06c270ec6" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongtermDebtTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_7fe99f7b-2a4c-41d0-ab86-381efd1c1e64" xlink:to="loc_us-gaap_LongtermDebtTypeAxis_bc13abf2-df06-4bf7-ac3a-65f06c270ec6" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_bc13abf2-df06-4bf7-ac3a-65f06c270ec6_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongtermDebtTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_bc13abf2-df06-4bf7-ac3a-65f06c270ec6" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_bc13abf2-df06-4bf7-ac3a-65f06c270ec6_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_b2cdc4cd-e32c-4eed-8fcf-1def73740ab7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongtermDebtTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_bc13abf2-df06-4bf7-ac3a-65f06c270ec6" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_b2cdc4cd-e32c-4eed-8fcf-1def73740ab7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LoansPayableMember_514a3059-ef43-4f68-b1fc-c601e642b822" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LoansPayableMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongtermDebtTypeDomain_b2cdc4cd-e32c-4eed-8fcf-1def73740ab7" xlink:to="loc_us-gaap_LoansPayableMember_514a3059-ef43-4f68-b1fc-c601e642b822" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentInKindPIKNoteMember_a930ba9e-2cb3-4039-b19a-96b27c5efb6f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PaymentInKindPIKNoteMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongtermDebtTypeDomain_b2cdc4cd-e32c-4eed-8fcf-1def73740ab7" xlink:to="loc_us-gaap_PaymentInKindPIKNoteMember_a930ba9e-2cb3-4039-b19a-96b27c5efb6f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityAxis_b775f830-d37f-449e-a0c9-aaa31e9bd7b3" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CreditFacilityAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_7fe99f7b-2a4c-41d0-ab86-381efd1c1e64" xlink:to="loc_us-gaap_CreditFacilityAxis_b775f830-d37f-449e-a0c9-aaa31e9bd7b3" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityDomain_b775f830-d37f-449e-a0c9-aaa31e9bd7b3_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CreditFacilityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_CreditFacilityAxis_b775f830-d37f-449e-a0c9-aaa31e9bd7b3" xlink:to="loc_us-gaap_CreditFacilityDomain_b775f830-d37f-449e-a0c9-aaa31e9bd7b3_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityDomain_6b0b1de9-987a-43b4-83ac-2b918c72ac1a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CreditFacilityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_CreditFacilityAxis_b775f830-d37f-449e-a0c9-aaa31e9bd7b3" xlink:to="loc_us-gaap_CreditFacilityDomain_6b0b1de9-987a-43b4-83ac-2b918c72ac1a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DelayedDrawTermLoanMember_0322a1a5-d7d9-4760-bb9a-8071bb7fde6d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DelayedDrawTermLoanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CreditFacilityDomain_6b0b1de9-987a-43b4-83ac-2b918c72ac1a" xlink:to="loc_us-gaap_DelayedDrawTermLoanMember_0322a1a5-d7d9-4760-bb9a-8071bb7fde6d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeAxis_020d8634-080f-4dfa-b4fc-18dfa0f2bf21" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SubsequentEventTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_7fe99f7b-2a4c-41d0-ab86-381efd1c1e64" xlink:to="loc_us-gaap_SubsequentEventTypeAxis_020d8634-080f-4dfa-b4fc-18dfa0f2bf21" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeDomain_020d8634-080f-4dfa-b4fc-18dfa0f2bf21_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SubsequentEventTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_SubsequentEventTypeAxis_020d8634-080f-4dfa-b4fc-18dfa0f2bf21" xlink:to="loc_us-gaap_SubsequentEventTypeDomain_020d8634-080f-4dfa-b4fc-18dfa0f2bf21_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeDomain_d76afe3a-6e8a-4560-8182-9c71feebef01" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SubsequentEventTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_SubsequentEventTypeAxis_020d8634-080f-4dfa-b4fc-18dfa0f2bf21" xlink:to="loc_us-gaap_SubsequentEventTypeDomain_d76afe3a-6e8a-4560-8182-9c71feebef01" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventMember_7330b8fb-b665-44bc-88f7-80c069237520" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SubsequentEventMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventTypeDomain_d76afe3a-6e8a-4560-8182-9c71feebef01" xlink:to="loc_us-gaap_SubsequentEventMember_7330b8fb-b665-44bc-88f7-80c069237520" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_22dc0c78-e361-453f-965f-cecfed119e5b" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_7fe99f7b-2a4c-41d0-ab86-381efd1c1e64" xlink:to="loc_srt_RangeAxis_22dc0c78-e361-453f-965f-cecfed119e5b" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_22dc0c78-e361-453f-965f-cecfed119e5b_default" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_22dc0c78-e361-453f-965f-cecfed119e5b" xlink:to="loc_srt_RangeMember_22dc0c78-e361-453f-965f-cecfed119e5b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_c2902a33-7751-4a08-a0d0-efff87be5e3d" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_22dc0c78-e361-453f-965f-cecfed119e5b" xlink:to="loc_srt_RangeMember_c2902a33-7751-4a08-a0d0-efff87be5e3d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_bff907bb-242d-43ec-8de8-d7c49888574b" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_MinimumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_c2902a33-7751-4a08-a0d0-efff87be5e3d" xlink:to="loc_srt_MinimumMember_bff907bb-242d-43ec-8de8-d7c49888574b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_ac5c0407-15f1-4197-b328-3b384d0e6c4b" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_c2902a33-7751-4a08-a0d0-efff87be5e3d" xlink:to="loc_srt_MaximumMember_ac5c0407-15f1-4197-b328-3b384d0e6c4b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromIssuanceOfLongTermDebt_dc3e45e3-2c0c-4b8d-96f8-5987c8519077" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ProceedsFromIssuanceOfLongTermDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_eaf5e6f3-b0a1-4d3e-89e2-2b17be709828" xlink:to="loc_us-gaap_ProceedsFromIssuanceOfLongTermDebt_dc3e45e3-2c0c-4b8d-96f8-5987c8519077" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityRemainingBorrowingCapacity_f1b7c17f-d1ca-482b-8593-de1f9ebfbfe8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LineOfCreditFacilityRemainingBorrowingCapacity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_eaf5e6f3-b0a1-4d3e-89e2-2b17be709828" xlink:to="loc_us-gaap_LineOfCreditFacilityRemainingBorrowingCapacity_f1b7c17f-d1ca-482b-8593-de1f9ebfbfe8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RepaymentsOfLongTermDebt_bc15f58e-18dd-431f-a9a1-a120d207507e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RepaymentsOfLongTermDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_eaf5e6f3-b0a1-4d3e-89e2-2b17be709828" xlink:to="loc_us-gaap_RepaymentsOfLongTermDebt_bc15f58e-18dd-431f-a9a1-a120d207507e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentBasisSpreadOnVariableRate1_2466dfc8-009b-4eec-8d56-a659fcddc3c1" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentBasisSpreadOnVariableRate1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_eaf5e6f3-b0a1-4d3e-89e2-2b17be709828" xlink:to="loc_us-gaap_DebtInstrumentBasisSpreadOnVariableRate1_2466dfc8-009b-4eec-8d56-a659fcddc3c1" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentInterestRateStatedPercentage_f826e5ba-4ec9-41af-9f8d-c6c41cc70c06" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentInterestRateStatedPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_eaf5e6f3-b0a1-4d3e-89e2-2b17be709828" xlink:to="loc_us-gaap_DebtInstrumentInterestRateStatedPercentage_f826e5ba-4ec9-41af-9f8d-c6c41cc70c06" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_DebtInstrumentStatedInterestRatePaidInKind_2d24f909-f670-4f21-8f8a-928ef7b30f84" xlink:href="exdx-20250331.xsd#exdx_DebtInstrumentStatedInterestRatePaidInKind"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_eaf5e6f3-b0a1-4d3e-89e2-2b17be709828" xlink:to="loc_exdx_DebtInstrumentStatedInterestRatePaidInKind_2d24f909-f670-4f21-8f8a-928ef7b30f84" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentInterestRateEffectivePercentage_6776dd25-0805-4674-aa46-4c48d8001341" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentInterestRateEffectivePercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_eaf5e6f3-b0a1-4d3e-89e2-2b17be709828" xlink:to="loc_us-gaap_DebtInstrumentInterestRateEffectivePercentage_6776dd25-0805-4674-aa46-4c48d8001341" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_DebtInstrumentNumberOfMonthlyInstallments_dcedff8c-8a0c-4b59-b96e-cb71db8aa3df" xlink:href="exdx-20250331.xsd#exdx_DebtInstrumentNumberOfMonthlyInstallments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_eaf5e6f3-b0a1-4d3e-89e2-2b17be709828" xlink:to="loc_exdx_DebtInstrumentNumberOfMonthlyInstallments_dcedff8c-8a0c-4b59-b96e-cb71db8aa3df" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentFeeAmount_2aa220ee-379c-4c89-9c69-a0ba96d4d8f7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentFeeAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_eaf5e6f3-b0a1-4d3e-89e2-2b17be709828" xlink:to="loc_us-gaap_DebtInstrumentFeeAmount_2aa220ee-379c-4c89-9c69-a0ba96d4d8f7" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_DebtInstrumentPaidInKindLoansIssued_0c59f1fb-5018-4c36-93f2-448c4544bcc1" xlink:href="exdx-20250331.xsd#exdx_DebtInstrumentPaidInKindLoansIssued"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_eaf5e6f3-b0a1-4d3e-89e2-2b17be709828" xlink:to="loc_exdx_DebtInstrumentPaidInKindLoansIssued_0c59f1fb-5018-4c36-93f2-448c4544bcc1" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_DebtInstrumentCovenantRevenuePerformancePeriod_38594c1a-6122-4682-80c3-7e445b7b01ab" xlink:href="exdx-20250331.xsd#exdx_DebtInstrumentCovenantRevenuePerformancePeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_eaf5e6f3-b0a1-4d3e-89e2-2b17be709828" xlink:to="loc_exdx_DebtInstrumentCovenantRevenuePerformancePeriod_38594c1a-6122-4682-80c3-7e445b7b01ab" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_DebtInstrumentCovenantNumberOfDaysToCureIfPerformanceMeasureIsNotMet_702d3bb6-25d1-4bcc-99c6-94506a9d1614" xlink:href="exdx-20250331.xsd#exdx_DebtInstrumentCovenantNumberOfDaysToCureIfPerformanceMeasureIsNotMet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_eaf5e6f3-b0a1-4d3e-89e2-2b17be709828" xlink:to="loc_exdx_DebtInstrumentCovenantNumberOfDaysToCureIfPerformanceMeasureIsNotMet_702d3bb6-25d1-4bcc-99c6-94506a9d1614" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_DebtInstrumentCovenantComplianceMinimumUnrestrictedCashBalance_9078546a-1ac2-4c57-bf18-47b3eaa6ee9b" xlink:href="exdx-20250331.xsd#exdx_DebtInstrumentCovenantComplianceMinimumUnrestrictedCashBalance"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_eaf5e6f3-b0a1-4d3e-89e2-2b17be709828" xlink:to="loc_exdx_DebtInstrumentCovenantComplianceMinimumUnrestrictedCashBalance_9078546a-1ac2-4c57-bf18-47b3eaa6ee9b" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_DebtInstrumentCovenantNonComplianceInterestRateIncreaseDecrease_0acb8f32-ca9c-4faa-9019-00c95f90df8c" xlink:href="exdx-20250331.xsd#exdx_DebtInstrumentCovenantNonComplianceInterestRateIncreaseDecrease"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_eaf5e6f3-b0a1-4d3e-89e2-2b17be709828" xlink:to="loc_exdx_DebtInstrumentCovenantNonComplianceInterestRateIncreaseDecrease_0acb8f32-ca9c-4faa-9019-00c95f90df8c" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromLongTermLinesOfCredit_03120a06-f66e-4548-9fad-4967c63f6779" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ProceedsFromLongTermLinesOfCredit"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_eaf5e6f3-b0a1-4d3e-89e2-2b17be709828" xlink:to="loc_us-gaap_ProceedsFromLongTermLinesOfCredit_03120a06-f66e-4548-9fad-4967c63f6779" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NotesPayable_7bade6e6-9ac0-41e8-884c-a208bd46d51b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NotesPayable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_eaf5e6f3-b0a1-4d3e-89e2-2b17be709828" xlink:to="loc_us-gaap_NotesPayable_7bade6e6-9ac0-41e8-884c-a208bd46d51b" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NotesPayableCurrent_e9f65581-1968-4e2d-8eba-4d6f2c56c37e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NotesPayableCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_eaf5e6f3-b0a1-4d3e-89e2-2b17be709828" xlink:to="loc_us-gaap_NotesPayableCurrent_e9f65581-1968-4e2d-8eba-4d6f2c56c37e" xlink:type="arc" order="16"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermNotesPayable_9e1dc6a3-b1c0-4116-9846-5552ef5215ba" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongTermNotesPayable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_eaf5e6f3-b0a1-4d3e-89e2-2b17be709828" xlink:to="loc_us-gaap_LongTermNotesPayable_9e1dc6a3-b1c0-4116-9846-5552ef5215ba" xlink:type="arc" order="17"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.exagen.com/role/CommitmentandContingenciesDetails" xlink:type="simple" xlink:href="exdx-20250331.xsd#CommitmentandContingenciesDetails"/>
  <link:definitionLink xlink:role="http://www.exagen.com/role/CommitmentandContingenciesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LossContingenciesLineItems_9a5ab631-705b-4489-a8d1-0d95c3d231bb" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LossContingenciesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LossContingenciesTable_1fe72768-cc10-4b7d-9f17-367ec2bca560" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LossContingenciesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_LossContingenciesLineItems_9a5ab631-705b-4489-a8d1-0d95c3d231bb" xlink:to="loc_us-gaap_LossContingenciesTable_1fe72768-cc10-4b7d-9f17-367ec2bca560" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_b509c855-1820-42f0-91b4-f79ba5f60b87" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_LossContingenciesTable_1fe72768-cc10-4b7d-9f17-367ec2bca560" xlink:to="loc_srt_RangeAxis_b509c855-1820-42f0-91b4-f79ba5f60b87" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_b509c855-1820-42f0-91b4-f79ba5f60b87_default" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_b509c855-1820-42f0-91b4-f79ba5f60b87" xlink:to="loc_srt_RangeMember_b509c855-1820-42f0-91b4-f79ba5f60b87_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_86e39ea8-6305-4fbb-8d2a-4832b8a484ff" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_b509c855-1820-42f0-91b4-f79ba5f60b87" xlink:to="loc_srt_RangeMember_86e39ea8-6305-4fbb-8d2a-4832b8a484ff" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_0668cdca-e70f-4407-a423-694dca2653cc" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_MinimumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_86e39ea8-6305-4fbb-8d2a-4832b8a484ff" xlink:to="loc_srt_MinimumMember_0668cdca-e70f-4407-a423-694dca2653cc" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_a931d4fc-d8f1-4f1f-9310-b52ba5c95883" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_86e39ea8-6305-4fbb-8d2a-4832b8a484ff" xlink:to="loc_srt_MaximumMember_a931d4fc-d8f1-4f1f-9310-b52ba5c95883" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_LitigationCaseAxis_9a7f02f9-586b-4278-a9b1-f9b08d439469" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_LitigationCaseAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_LossContingenciesTable_1fe72768-cc10-4b7d-9f17-367ec2bca560" xlink:to="loc_srt_LitigationCaseAxis_9a7f02f9-586b-4278-a9b1-f9b08d439469" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_LitigationCaseTypeDomain_9a7f02f9-586b-4278-a9b1-f9b08d439469_default" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_LitigationCaseTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_LitigationCaseAxis_9a7f02f9-586b-4278-a9b1-f9b08d439469" xlink:to="loc_srt_LitigationCaseTypeDomain_9a7f02f9-586b-4278-a9b1-f9b08d439469_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_LitigationCaseTypeDomain_a19510b3-7d26-42b9-8f25-a7f3e71b52f4" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_LitigationCaseTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_LitigationCaseAxis_9a7f02f9-586b-4278-a9b1-f9b08d439469" xlink:to="loc_srt_LitigationCaseTypeDomain_a19510b3-7d26-42b9-8f25-a7f3e71b52f4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_USDepartmentOfJusticeCaseMember_8cd4c535-9c68-4f5d-b22c-cbe1968bad50" xlink:href="exdx-20250331.xsd#exdx_USDepartmentOfJusticeCaseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_LitigationCaseTypeDomain_a19510b3-7d26-42b9-8f25-a7f3e71b52f4" xlink:to="loc_exdx_USDepartmentOfJusticeCaseMember_8cd4c535-9c68-4f5d-b22c-cbe1968bad50" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LitigationStatusAxis_a0131a5a-0e99-4f00-a388-ee79774b1460" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LitigationStatusAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_LossContingenciesTable_1fe72768-cc10-4b7d-9f17-367ec2bca560" xlink:to="loc_us-gaap_LitigationStatusAxis_a0131a5a-0e99-4f00-a388-ee79774b1460" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LitigationStatusDomain_a0131a5a-0e99-4f00-a388-ee79774b1460_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LitigationStatusDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_LitigationStatusAxis_a0131a5a-0e99-4f00-a388-ee79774b1460" xlink:to="loc_us-gaap_LitigationStatusDomain_a0131a5a-0e99-4f00-a388-ee79774b1460_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LitigationStatusDomain_3ea1d35c-69ad-45f5-9da7-d4dfed664a3a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LitigationStatusDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_LitigationStatusAxis_a0131a5a-0e99-4f00-a388-ee79774b1460" xlink:to="loc_us-gaap_LitigationStatusDomain_3ea1d35c-69ad-45f5-9da7-d4dfed664a3a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SettledLitigationMember_252a1716-6764-47fd-a28a-18c6ed499aac" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SettledLitigationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LitigationStatusDomain_3ea1d35c-69ad-45f5-9da7-d4dfed664a3a" xlink:to="loc_us-gaap_SettledLitigationMember_252a1716-6764-47fd-a28a-18c6ed499aac" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_8de5b84a-82a5-436e-a76a-1cc708fcca10" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_LossContingenciesTable_1fe72768-cc10-4b7d-9f17-367ec2bca560" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_8de5b84a-82a5-436e-a76a-1cc708fcca10" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_8de5b84a-82a5-436e-a76a-1cc708fcca10_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_8de5b84a-82a5-436e-a76a-1cc708fcca10" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_8de5b84a-82a5-436e-a76a-1cc708fcca10_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_ca192276-aa00-43ed-b7d1-f56efec5f179" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_8de5b84a-82a5-436e-a76a-1cc708fcca10" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_ca192276-aa00-43ed-b7d1-f56efec5f179" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LicenseAgreementTermsMember_404f0083-6839-4a2f-8e34-efc7e2251ff1" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LicenseAgreementTermsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_ca192276-aa00-43ed-b7d1-f56efec5f179" xlink:to="loc_us-gaap_LicenseAgreementTermsMember_404f0083-6839-4a2f-8e34-efc7e2251ff1" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_RoyaltyObligationPercentageOfSales_6872eeb7-8ecd-486d-aad9-124bd17dc441" xlink:href="exdx-20250331.xsd#exdx_RoyaltyObligationPercentageOfSales"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LossContingenciesLineItems_9a5ab631-705b-4489-a8d1-0d95c3d231bb" xlink:to="loc_exdx_RoyaltyObligationPercentageOfSales_6872eeb7-8ecd-486d-aad9-124bd17dc441" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_PurchaseObligationAmendedSupplyAgreementNumberOfSuppliers_5d5b3c82-ccf5-49b6-8f3b-611b7c728209" xlink:href="exdx-20250331.xsd#exdx_PurchaseObligationAmendedSupplyAgreementNumberOfSuppliers"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LossContingenciesLineItems_9a5ab631-705b-4489-a8d1-0d95c3d231bb" xlink:to="loc_exdx_PurchaseObligationAmendedSupplyAgreementNumberOfSuppliers_5d5b3c82-ccf5-49b6-8f3b-611b7c728209" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PurchaseObligationFutureMinimumPaymentsRemainderOfFiscalYear_07298d82-0684-4004-a659-820c4b53b9c5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PurchaseObligationFutureMinimumPaymentsRemainderOfFiscalYear"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LossContingenciesLineItems_9a5ab631-705b-4489-a8d1-0d95c3d231bb" xlink:to="loc_us-gaap_PurchaseObligationFutureMinimumPaymentsRemainderOfFiscalYear_07298d82-0684-4004-a659-820c4b53b9c5" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsForLegalSettlements_1e888a5f-7ae5-419d-8399-961fa6cbdf1d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PaymentsForLegalSettlements"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LossContingenciesLineItems_9a5ab631-705b-4489-a8d1-0d95c3d231bb" xlink:to="loc_us-gaap_PaymentsForLegalSettlements_1e888a5f-7ae5-419d-8399-961fa6cbdf1d" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.exagen.com/role/FairValueMeasurementsNarrativeDetails" xlink:type="simple" xlink:href="exdx-20250331.xsd#FairValueMeasurementsNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.exagen.com/role/FairValueMeasurementsNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesLineItems_9fac89a9-3d73-4983-aaf0-9d3b15f8dadc" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesTable_612513f1-89e7-4933-9d68-93e456265092" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesLineItems_9fac89a9-3d73-4983-aaf0-9d3b15f8dadc" xlink:to="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesTable_612513f1-89e7-4933-9d68-93e456265092" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentAxis_d34c977d-d614-431f-bef1-371b8fd30e5c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesTable_612513f1-89e7-4933-9d68-93e456265092" xlink:to="loc_us-gaap_DebtInstrumentAxis_d34c977d-d614-431f-bef1-371b8fd30e5c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_d34c977d-d614-431f-bef1-371b8fd30e5c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DebtInstrumentAxis_d34c977d-d614-431f-bef1-371b8fd30e5c" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_d34c977d-d614-431f-bef1-371b8fd30e5c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_d3630b98-a94e-4a56-ba62-94aadd890eef" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DebtInstrumentAxis_d34c977d-d614-431f-bef1-371b8fd30e5c" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_d3630b98-a94e-4a56-ba62-94aadd890eef" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_AmendedLoanAgreementMember_8f4edbda-9786-495d-9d3d-e2a909fe4735" xlink:href="exdx-20250331.xsd#exdx_AmendedLoanAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_d3630b98-a94e-4a56-ba62-94aadd890eef" xlink:to="loc_exdx_AmendedLoanAgreementMember_8f4edbda-9786-495d-9d3d-e2a909fe4735" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_A2017TermLoanMember_6ab124f2-e4da-4bd4-a11d-bb3faeb4a522" xlink:href="exdx-20250331.xsd#exdx_A2017TermLoanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_d3630b98-a94e-4a56-ba62-94aadd890eef" xlink:to="loc_exdx_A2017TermLoanMember_6ab124f2-e4da-4bd4-a11d-bb3faeb4a522" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_EquipmentNotesPayableMember_ee2cfe6f-02c9-432d-bd61-8ef9bbaae9bb" xlink:href="exdx-20250331.xsd#exdx_EquipmentNotesPayableMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_d3630b98-a94e-4a56-ba62-94aadd890eef" xlink:to="loc_exdx_EquipmentNotesPayableMember_ee2cfe6f-02c9-432d-bd61-8ef9bbaae9bb" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_4e272eca-b63c-4d0e-a0cc-d56691c27326" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesTable_612513f1-89e7-4933-9d68-93e456265092" xlink:to="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_4e272eca-b63c-4d0e-a0cc-d56691c27326" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_4e272eca-b63c-4d0e-a0cc-d56691c27326_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_4e272eca-b63c-4d0e-a0cc-d56691c27326" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_4e272eca-b63c-4d0e-a0cc-d56691c27326_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_4f71f896-f172-409b-a8b5-ec60b1499982" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_4e272eca-b63c-4d0e-a0cc-d56691c27326" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_4f71f896-f172-409b-a8b5-ec60b1499982" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel2Member_ac7b8f5f-976e-41f3-a5e3-5ecac6307a3f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueInputsLevel2Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_4f71f896-f172-409b-a8b5-ec60b1499982" xlink:to="loc_us-gaap_FairValueInputsLevel2Member_ac7b8f5f-976e-41f3-a5e3-5ecac6307a3f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByMeasurementFrequencyAxis_58b49a05-fceb-444d-96be-32ad9a03c065" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueByMeasurementFrequencyAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesTable_612513f1-89e7-4933-9d68-93e456265092" xlink:to="loc_us-gaap_FairValueByMeasurementFrequencyAxis_58b49a05-fceb-444d-96be-32ad9a03c065" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementFrequencyDomain_58b49a05-fceb-444d-96be-32ad9a03c065_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueMeasurementFrequencyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByMeasurementFrequencyAxis_58b49a05-fceb-444d-96be-32ad9a03c065" xlink:to="loc_us-gaap_FairValueMeasurementFrequencyDomain_58b49a05-fceb-444d-96be-32ad9a03c065_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementFrequencyDomain_704ce6b6-0252-4d2c-b594-6ff37e4ff457" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueMeasurementFrequencyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByMeasurementFrequencyAxis_58b49a05-fceb-444d-96be-32ad9a03c065" xlink:to="loc_us-gaap_FairValueMeasurementFrequencyDomain_704ce6b6-0252-4d2c-b594-6ff37e4ff457" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsRecurringMember_7d380f22-f107-48c9-8964-003ddd72b315" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueMeasurementsRecurringMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementFrequencyDomain_704ce6b6-0252-4d2c-b594-6ff37e4ff457" xlink:to="loc_us-gaap_FairValueMeasurementsRecurringMember_7d380f22-f107-48c9-8964-003ddd72b315" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentFairValue_fcbfd7e6-0d23-4599-bf06-b5fc51642a4b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesLineItems_9fac89a9-3d73-4983-aaf0-9d3b15f8dadc" xlink:to="loc_us-gaap_DebtInstrumentFairValue_fcbfd7e6-0d23-4599-bf06-b5fc51642a4b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebt_d662d66c-ddb4-4e3f-857d-81157270e4b8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongTermDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesLineItems_9fac89a9-3d73-4983-aaf0-9d3b15f8dadc" xlink:to="loc_us-gaap_LongTermDebt_d662d66c-ddb4-4e3f-857d-81157270e4b8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NotesPayable_4d7ef5b9-8621-4ec6-95c3-8546a53ce048" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NotesPayable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesLineItems_9fac89a9-3d73-4983-aaf0-9d3b15f8dadc" xlink:to="loc_us-gaap_NotesPayable_4d7ef5b9-8621-4ec6-95c3-8546a53ce048" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.exagen.com/role/FairValueMeasurementsFinancialInstrumentsDetails" xlink:type="simple" xlink:href="exdx-20250331.xsd#FairValueMeasurementsFinancialInstrumentsDetails"/>
  <link:definitionLink xlink:role="http://www.exagen.com/role/FairValueMeasurementsFinancialInstrumentsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesLineItems_af0ac170-533e-4064-89a7-ced2ab190d7d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesTable_20f5fbd3-28a8-43af-a156-bd85486a94d9" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesLineItems_af0ac170-533e-4064-89a7-ced2ab190d7d" xlink:to="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesTable_20f5fbd3-28a8-43af-a156-bd85486a94d9" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByMeasurementFrequencyAxis_35b8d5ed-2ff6-45e5-8db8-892d6117e827" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueByMeasurementFrequencyAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesTable_20f5fbd3-28a8-43af-a156-bd85486a94d9" xlink:to="loc_us-gaap_FairValueByMeasurementFrequencyAxis_35b8d5ed-2ff6-45e5-8db8-892d6117e827" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementFrequencyDomain_35b8d5ed-2ff6-45e5-8db8-892d6117e827_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueMeasurementFrequencyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByMeasurementFrequencyAxis_35b8d5ed-2ff6-45e5-8db8-892d6117e827" xlink:to="loc_us-gaap_FairValueMeasurementFrequencyDomain_35b8d5ed-2ff6-45e5-8db8-892d6117e827_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementFrequencyDomain_791b7e82-fc8e-48db-bb94-6d96a5389c4e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueMeasurementFrequencyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByMeasurementFrequencyAxis_35b8d5ed-2ff6-45e5-8db8-892d6117e827" xlink:to="loc_us-gaap_FairValueMeasurementFrequencyDomain_791b7e82-fc8e-48db-bb94-6d96a5389c4e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsRecurringMember_803a954f-36d7-40cd-9807-1d1283ba8095" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueMeasurementsRecurringMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementFrequencyDomain_791b7e82-fc8e-48db-bb94-6d96a5389c4e" xlink:to="loc_us-gaap_FairValueMeasurementsRecurringMember_803a954f-36d7-40cd-9807-1d1283ba8095" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_79b0287a-573e-457d-ae0c-bf86d42512d9" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesTable_20f5fbd3-28a8-43af-a156-bd85486a94d9" xlink:to="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_79b0287a-573e-457d-ae0c-bf86d42512d9" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_79b0287a-573e-457d-ae0c-bf86d42512d9_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_79b0287a-573e-457d-ae0c-bf86d42512d9" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_79b0287a-573e-457d-ae0c-bf86d42512d9_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_f4911bdd-5a06-4879-a649-d5a0081abe9c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_79b0287a-573e-457d-ae0c-bf86d42512d9" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_f4911bdd-5a06-4879-a649-d5a0081abe9c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel1Member_ef65aca4-5b80-4025-80e8-0ed2b2cb13f3" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueInputsLevel1Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_f4911bdd-5a06-4879-a649-d5a0081abe9c" xlink:to="loc_us-gaap_FairValueInputsLevel1Member_ef65aca4-5b80-4025-80e8-0ed2b2cb13f3" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel2Member_1bc37d73-f0b6-43d4-841c-dc4356beeac0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueInputsLevel2Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_f4911bdd-5a06-4879-a649-d5a0081abe9c" xlink:to="loc_us-gaap_FairValueInputsLevel2Member_1bc37d73-f0b6-43d4-841c-dc4356beeac0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel3Member_4c3de034-b7a4-44c4-bead-631086b97e04" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueInputsLevel3Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_f4911bdd-5a06-4879-a649-d5a0081abe9c" xlink:to="loc_us-gaap_FairValueInputsLevel3Member_4c3de034-b7a4-44c4-bead-631086b97e04" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_fb80b3a2-33e6-4d3c-9cc3-72603bf62fbb" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesTable_20f5fbd3-28a8-43af-a156-bd85486a94d9" xlink:to="loc_us-gaap_FinancialInstrumentAxis_fb80b3a2-33e6-4d3c-9cc3-72603bf62fbb" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_fb80b3a2-33e6-4d3c-9cc3-72603bf62fbb_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_fb80b3a2-33e6-4d3c-9cc3-72603bf62fbb" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_fb80b3a2-33e6-4d3c-9cc3-72603bf62fbb_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_802ac817-7a94-4916-bce2-b4640220ba73" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_fb80b3a2-33e6-4d3c-9cc3-72603bf62fbb" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_802ac817-7a94-4916-bce2-b4640220ba73" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MoneyMarketFundsMember_867b6d0c-24ad-48df-b741-87693946fdce" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_MoneyMarketFundsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_802ac817-7a94-4916-bce2-b4640220ba73" xlink:to="loc_us-gaap_MoneyMarketFundsMember_867b6d0c-24ad-48df-b741-87693946fdce" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsFairValueDisclosureAbstract_cf149d74-6f16-4e61-b09c-18005b85c838" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AssetsFairValueDisclosureAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisValuationTechniquesLineItems_af0ac170-533e-4064-89a7-ced2ab190d7d" xlink:to="loc_us-gaap_AssetsFairValueDisclosureAbstract_cf149d74-6f16-4e61-b09c-18005b85c838" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsFairValueDisclosure_4a2b740a-a324-43b5-87c7-aea207af7206" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CashAndCashEquivalentsFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsFairValueDisclosureAbstract_cf149d74-6f16-4e61-b09c-18005b85c838" xlink:to="loc_us-gaap_CashAndCashEquivalentsFairValueDisclosure_4a2b740a-a324-43b5-87c7-aea207af7206" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.exagen.com/role/StockholdersEquityNarrativeDetails" xlink:type="simple" xlink:href="exdx-20250331.xsd#StockholdersEquityNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.exagen.com/role/StockholdersEquityNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockLineItems_4ff55cfd-00e3-44bf-b064-822c28ebb1d5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ClassOfStockLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfStockByClassTable_e901fe57-7eb2-41bc-b11e-fdac51207e09" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfStockByClassTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ClassOfStockLineItems_4ff55cfd-00e3-44bf-b064-822c28ebb1d5" xlink:to="loc_us-gaap_ScheduleOfStockByClassTable_e901fe57-7eb2-41bc-b11e-fdac51207e09" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsidiarySaleOfStockAxis_812ef531-dc75-46ce-a96d-cefb2bec0064" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SubsidiarySaleOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfStockByClassTable_e901fe57-7eb2-41bc-b11e-fdac51207e09" xlink:to="loc_us-gaap_SubsidiarySaleOfStockAxis_812ef531-dc75-46ce-a96d-cefb2bec0064" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_812ef531-dc75-46ce-a96d-cefb2bec0064_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_812ef531-dc75-46ce-a96d-cefb2bec0064" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_812ef531-dc75-46ce-a96d-cefb2bec0064_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_48f0894d-7925-466a-b7f0-863c96374bcd" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_812ef531-dc75-46ce-a96d-cefb2bec0064" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_48f0894d-7925-466a-b7f0-863c96374bcd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_ShelfRegistrationStatementMember_795b1d01-6b93-4677-85f6-37795b5182c7" xlink:href="exdx-20250331.xsd#exdx_ShelfRegistrationStatementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SaleOfStockNameOfTransactionDomain_48f0894d-7925-466a-b7f0-863c96374bcd" xlink:to="loc_exdx_ShelfRegistrationStatementMember_795b1d01-6b93-4677-85f6-37795b5182c7" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_CowenEquityDistributionAgreementMember_4cfba5a1-ceca-47f9-a4b4-ce91ed774469" xlink:href="exdx-20250331.xsd#exdx_CowenEquityDistributionAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SaleOfStockNameOfTransactionDomain_48f0894d-7925-466a-b7f0-863c96374bcd" xlink:to="loc_exdx_CowenEquityDistributionAgreementMember_4cfba5a1-ceca-47f9-a4b4-ce91ed774469" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_SaleOfStockAuthorizedAmount_09732d8d-baec-4a9f-be47-4cb19dd3b707" xlink:href="exdx-20250331.xsd#exdx_SaleOfStockAuthorizedAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_4ff55cfd-00e3-44bf-b064-822c28ebb1d5" xlink:to="loc_exdx_SaleOfStockAuthorizedAmount_09732d8d-baec-4a9f-be47-4cb19dd3b707" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_SaleOfStockRemainingAuthorizedAmount_43f69dd2-7cf4-4dc6-ab45-a7c4bd70364d" xlink:href="exdx-20250331.xsd#exdx_SaleOfStockRemainingAuthorizedAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_4ff55cfd-00e3-44bf-b064-822c28ebb1d5" xlink:to="loc_exdx_SaleOfStockRemainingAuthorizedAmount_43f69dd2-7cf4-4dc6-ab45-a7c4bd70364d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockConsiderationReceivedOnTransaction_5012552c-232e-46cc-b04c-a9d1c2360d1b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SaleOfStockConsiderationReceivedOnTransaction"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_4ff55cfd-00e3-44bf-b064-822c28ebb1d5" xlink:to="loc_us-gaap_SaleOfStockConsiderationReceivedOnTransaction_5012552c-232e-46cc-b04c-a9d1c2360d1b" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.exagen.com/role/StockholdersEquityOutstandingWarrantsDetails" xlink:type="simple" xlink:href="exdx-20250331.xsd#StockholdersEquityOutstandingWarrantsDetails"/>
  <link:definitionLink xlink:role="http://www.exagen.com/role/StockholdersEquityOutstandingWarrantsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockLineItems_0a810801-261d-4146-b94e-d540dfc6a950" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ClassOfStockLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfStockByClassTable_43b1d2a9-1188-4c52-9f53-84ee5a8db59e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfStockByClassTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ClassOfStockLineItems_0a810801-261d-4146-b94e-d540dfc6a950" xlink:to="loc_us-gaap_ScheduleOfStockByClassTable_43b1d2a9-1188-4c52-9f53-84ee5a8db59e" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightAxis_9ba97f24-41bb-44bd-8087-3da88f2973b0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ClassOfWarrantOrRightAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfStockByClassTable_43b1d2a9-1188-4c52-9f53-84ee5a8db59e" xlink:to="loc_us-gaap_ClassOfWarrantOrRightAxis_9ba97f24-41bb-44bd-8087-3da88f2973b0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightDomain_9ba97f24-41bb-44bd-8087-3da88f2973b0_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ClassOfWarrantOrRightDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ClassOfWarrantOrRightAxis_9ba97f24-41bb-44bd-8087-3da88f2973b0" xlink:to="loc_us-gaap_ClassOfWarrantOrRightDomain_9ba97f24-41bb-44bd-8087-3da88f2973b0_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightDomain_996eec95-e076-42a5-a974-7ed625baa636" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ClassOfWarrantOrRightDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ClassOfWarrantOrRightAxis_9ba97f24-41bb-44bd-8087-3da88f2973b0" xlink:to="loc_us-gaap_ClassOfWarrantOrRightDomain_996eec95-e076-42a5-a974-7ed625baa636" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_ExpirationJan192026Member_706a4bdf-7a80-424b-9d79-f6a73aae988f" xlink:href="exdx-20250331.xsd#exdx_ExpirationJan192026Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightDomain_996eec95-e076-42a5-a974-7ed625baa636" xlink:to="loc_exdx_ExpirationJan192026Member_706a4bdf-7a80-424b-9d79-f6a73aae988f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_ExpirationMar312026Member_df4c1e01-5c43-475a-82e6-b58a5ce828ce" xlink:href="exdx-20250331.xsd#exdx_ExpirationMar312026Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightDomain_996eec95-e076-42a5-a974-7ed625baa636" xlink:to="loc_exdx_ExpirationMar312026Member_df4c1e01-5c43-475a-82e6-b58a5ce828ce" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_ExpirationApr12026Member_9a805edb-434b-4e3c-b400-73f88a491428" xlink:href="exdx-20250331.xsd#exdx_ExpirationApr12026Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightDomain_996eec95-e076-42a5-a974-7ed625baa636" xlink:to="loc_exdx_ExpirationApr12026Member_9a805edb-434b-4e3c-b400-73f88a491428" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_ExpirationDec72025Member_6c4f6b76-909e-4d3d-a4ae-0debccef25ab" xlink:href="exdx-20250331.xsd#exdx_ExpirationDec72025Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightDomain_996eec95-e076-42a5-a974-7ed625baa636" xlink:to="loc_exdx_ExpirationDec72025Member_6c4f6b76-909e-4d3d-a4ae-0debccef25ab" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_NoExpirationMember_33f03dd6-715e-4d21-aed7-16d50289d72a" xlink:href="exdx-20250331.xsd#exdx_NoExpirationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightDomain_996eec95-e076-42a5-a974-7ed625baa636" xlink:to="loc_exdx_NoExpirationMember_33f03dd6-715e-4d21-aed7-16d50289d72a" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightOutstanding_f1f73bac-d9f2-4e22-878f-dcef32bade55" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ClassOfWarrantOrRightOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_0a810801-261d-4146-b94e-d540dfc6a950" xlink:to="loc_us-gaap_ClassOfWarrantOrRightOutstanding_f1f73bac-d9f2-4e22-878f-dcef32bade55" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1_65b00cba-62c0-4a79-b7e0-1e9eca1c93eb" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_0a810801-261d-4146-b94e-d540dfc6a950" xlink:to="loc_us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1_65b00cba-62c0-4a79-b7e0-1e9eca1c93eb" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.exagen.com/role/StockOptionPlanNarrativeDetails" xlink:type="simple" xlink:href="exdx-20250331.xsd#StockOptionPlanNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.exagen.com/role/StockOptionPlanNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_30f45548-ac7f-40a2-b59f-3771a1668b53" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_6bd8354e-7d8f-4fa5-90a9-c6236a186a31" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_30f45548-ac7f-40a2-b59f-3771a1668b53" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_6bd8354e-7d8f-4fa5-90a9-c6236a186a31" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_2c1031f0-44ae-4733-8145-a26c79f7e53c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_6bd8354e-7d8f-4fa5-90a9-c6236a186a31" xlink:to="loc_us-gaap_AwardTypeAxis_2c1031f0-44ae-4733-8145-a26c79f7e53c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_2c1031f0-44ae-4733-8145-a26c79f7e53c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_2c1031f0-44ae-4733-8145-a26c79f7e53c" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_2c1031f0-44ae-4733-8145-a26c79f7e53c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_1620a073-08c7-4249-b24e-72bc8bd4ac59" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_2c1031f0-44ae-4733-8145-a26c79f7e53c" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_1620a073-08c7-4249-b24e-72bc8bd4ac59" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockOptionMember_72007341-03be-4af1-8252-4cba2645e6d0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EmployeeStockOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_1620a073-08c7-4249-b24e-72bc8bd4ac59" xlink:to="loc_us-gaap_EmployeeStockOptionMember_72007341-03be-4af1-8252-4cba2645e6d0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockMember_6459c7b9-3aff-4556-9767-64f9d02c4e03" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EmployeeStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_1620a073-08c7-4249-b24e-72bc8bd4ac59" xlink:to="loc_us-gaap_EmployeeStockMember_6459c7b9-3aff-4556-9767-64f9d02c4e03" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_CommonSharesAvailableForGrantUnderThe2019PlanMember_1417f7e2-2405-4b5f-b7a2-4a6bf70619b5" xlink:href="exdx-20250331.xsd#exdx_CommonSharesAvailableForGrantUnderThe2019PlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_1620a073-08c7-4249-b24e-72bc8bd4ac59" xlink:to="loc_exdx_CommonSharesAvailableForGrantUnderThe2019PlanMember_1417f7e2-2405-4b5f-b7a2-4a6bf70619b5" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_067cd77b-b661-42f1-ab83-b540170041bd" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_1620a073-08c7-4249-b24e-72bc8bd4ac59" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_067cd77b-b661-42f1-ab83-b540170041bd" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameAxis_e5dd1108-1ba6-4992-aa25-38bb890ce057" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PlanNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_6bd8354e-7d8f-4fa5-90a9-c6236a186a31" xlink:to="loc_us-gaap_PlanNameAxis_e5dd1108-1ba6-4992-aa25-38bb890ce057" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_e5dd1108-1ba6-4992-aa25-38bb890ce057_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PlanNameAxis_e5dd1108-1ba6-4992-aa25-38bb890ce057" xlink:to="loc_us-gaap_PlanNameDomain_e5dd1108-1ba6-4992-aa25-38bb890ce057_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_57618476-d754-4dea-bd5c-ca5270144142" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PlanNameAxis_e5dd1108-1ba6-4992-aa25-38bb890ce057" xlink:to="loc_us-gaap_PlanNameDomain_57618476-d754-4dea-bd5c-ca5270144142" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_IncentiveAwardPlan2019Member_b6f9fd5a-d81a-4c72-984a-5a86a77147bf" xlink:href="exdx-20250331.xsd#exdx_IncentiveAwardPlan2019Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_57618476-d754-4dea-bd5c-ca5270144142" xlink:to="loc_exdx_IncentiveAwardPlan2019Member_b6f9fd5a-d81a-4c72-984a-5a86a77147bf" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod_38198713-4373-41f9-9487-cbfba752190d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_30f45548-ac7f-40a2-b59f-3771a1668b53" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod_38198713-4373-41f9-9487-cbfba752190d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_2c6f7b5c-19a0-4117-aa54-241d7a69be51" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_30f45548-ac7f-40a2-b59f-3771a1668b53" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_2c6f7b5c-19a0-4117-aa54-241d7a69be51" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalSharesAuthorizedPercentage_bb17bc99-f61f-48d5-aec7-fe9af6ababc9" xlink:href="exdx-20250331.xsd#exdx_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalSharesAuthorizedPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_30f45548-ac7f-40a2-b59f-3771a1668b53" xlink:to="loc_exdx_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalSharesAuthorizedPercentage_bb17bc99-f61f-48d5-aec7-fe9af6ababc9" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_ShareBasedCompensationArrangementByShareBasedPaymentAwardIncreaseDecreaseInNumberOfSharesAuthorized_97896d63-4633-44cd-8229-7e2944220dc8" xlink:href="exdx-20250331.xsd#exdx_ShareBasedCompensationArrangementByShareBasedPaymentAwardIncreaseDecreaseInNumberOfSharesAuthorized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_30f45548-ac7f-40a2-b59f-3771a1668b53" xlink:to="loc_exdx_ShareBasedCompensationArrangementByShareBasedPaymentAwardIncreaseDecreaseInNumberOfSharesAuthorized_97896d63-4633-44cd-8229-7e2944220dc8" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockCapitalSharesReservedForFutureIssuance_294559ee-cf19-4505-b2c6-547d9da67bef" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CommonStockCapitalSharesReservedForFutureIssuance"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_30f45548-ac7f-40a2-b59f-3771a1668b53" xlink:to="loc_us-gaap_CommonStockCapitalSharesReservedForFutureIssuance_294559ee-cf19-4505-b2c6-547d9da67bef" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_d50de02c-c159-4552-b26e-3996975302ba" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_30f45548-ac7f-40a2-b59f-3771a1668b53" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_d50de02c-c159-4552-b26e-3996975302ba" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardEquityInstrumentsOtherThanOptionsAggregateIntrinsicValueVested_de1a90c6-6950-4153-9814-591319c5c370" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardEquityInstrumentsOtherThanOptionsAggregateIntrinsicValueVested"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_30f45548-ac7f-40a2-b59f-3771a1668b53" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardEquityInstrumentsOtherThanOptionsAggregateIntrinsicValueVested_de1a90c6-6950-4153-9814-591319c5c370" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_71bee08b-c833-419f-aab7-3cd0779e9de9" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_30f45548-ac7f-40a2-b59f-3771a1668b53" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_71bee08b-c833-419f-aab7-3cd0779e9de9" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognized_737ea26b-bdf6-4b41-a5dd-b1676cf128d0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_30f45548-ac7f-40a2-b59f-3771a1668b53" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognized_737ea26b-bdf6-4b41-a5dd-b1676cf128d0" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_78cb451d-b225-433e-93a4-b239f3f74f0a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_30f45548-ac7f-40a2-b59f-3771a1668b53" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_78cb451d-b225-433e-93a4-b239f3f74f0a" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross_3423f19d-29e0-4524-9c6f-e59b27d3af93" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_30f45548-ac7f-40a2-b59f-3771a1668b53" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross_3423f19d-29e0-4524-9c6f-e59b27d3af93" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_73874cc6-0fdb-44e2-8cf9-6e2f467e3349" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_30f45548-ac7f-40a2-b59f-3771a1668b53" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_73874cc6-0fdb-44e2-8cf9-6e2f467e3349" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate_77594390-b0f1-4fa9-a7c5-f8fb9835e48a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_30f45548-ac7f-40a2-b59f-3771a1668b53" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate_77594390-b0f1-4fa9-a7c5-f8fb9835e48a" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans_3b9ad95f-6859-46eb-99df-afd0e52a8553" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_30f45548-ac7f-40a2-b59f-3771a1668b53" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans_3b9ad95f-6859-46eb-99df-afd0e52a8553" xlink:type="arc" order="13"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.exagen.com/role/StockOptionPlanRestrictedStockUnitsDetails" xlink:type="simple" xlink:href="exdx-20250331.xsd#StockOptionPlanRestrictedStockUnitsDetails"/>
  <link:definitionLink xlink:role="http://www.exagen.com/role/StockOptionPlanRestrictedStockUnitsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_788ed6e3-1abb-46ba-a5be-214d8af27b56" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_cef218d5-b210-4fca-817a-0e4b7c7bb26c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_788ed6e3-1abb-46ba-a5be-214d8af27b56" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_cef218d5-b210-4fca-817a-0e4b7c7bb26c" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_173291ce-93cb-40ed-9605-7f0901b5985a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_cef218d5-b210-4fca-817a-0e4b7c7bb26c" xlink:to="loc_us-gaap_AwardTypeAxis_173291ce-93cb-40ed-9605-7f0901b5985a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_173291ce-93cb-40ed-9605-7f0901b5985a_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_173291ce-93cb-40ed-9605-7f0901b5985a" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_173291ce-93cb-40ed-9605-7f0901b5985a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_c9595a78-b7ef-40d2-a5bc-d92f946121ff" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_173291ce-93cb-40ed-9605-7f0901b5985a" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_c9595a78-b7ef-40d2-a5bc-d92f946121ff" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_5b8db57a-e500-4911-b020-a79ef48c8560" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_c9595a78-b7ef-40d2-a5bc-d92f946121ff" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_5b8db57a-e500-4911-b020-a79ef48c8560" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_a3a38bba-1899-4e5f-9d97-ef3f8af8e83f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_788ed6e3-1abb-46ba-a5be-214d8af27b56" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_a3a38bba-1899-4e5f-9d97-ef3f8af8e83f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_748c0551-ba75-412f-9a42-88299cd1a8b0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_a3a38bba-1899-4e5f-9d97-ef3f8af8e83f" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_748c0551-ba75-412f-9a42-88299cd1a8b0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_0e5c98e0-cb70-4564-a4d1-83daaea2fce7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_a3a38bba-1899-4e5f-9d97-ef3f8af8e83f" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_0e5c98e0-cb70-4564-a4d1-83daaea2fce7" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod_0e2e9e08-7765-4591-8283-1cbf1a1e57de" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_a3a38bba-1899-4e5f-9d97-ef3f8af8e83f" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod_0e2e9e08-7765-4591-8283-1cbf1a1e57de" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod_357db947-7391-4cce-b46e-bf3f0ee366b2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_a3a38bba-1899-4e5f-9d97-ef3f8af8e83f" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod_357db947-7391-4cce-b46e-bf3f0ee366b2" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_a733715f-03a5-4cd0-92bd-88d16aac9637" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_00345943-163a-44df-b875-fc30385d8ff8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_788ed6e3-1abb-46ba-a5be-214d8af27b56" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_00345943-163a-44df-b875-fc30385d8ff8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_8780d230-93db-4feb-ab56-da83a2103383" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_00345943-163a-44df-b875-fc30385d8ff8" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_8780d230-93db-4feb-ab56-da83a2103383" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_38192953-6c40-4ab2-bd50-e4ae3dac3601" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_00345943-163a-44df-b875-fc30385d8ff8" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_38192953-6c40-4ab2-bd50-e4ae3dac3601" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue_980bd47b-521c-4fab-9c82-8db84755bee6" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_00345943-163a-44df-b875-fc30385d8ff8" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue_980bd47b-521c-4fab-9c82-8db84755bee6" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue_592ec453-ecc0-46a4-b9a7-ab2ced871200" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_00345943-163a-44df-b875-fc30385d8ff8" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue_592ec453-ecc0-46a4-b9a7-ab2ced871200" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_6928dad2-de06-4dbd-b754-1f86050a71ae" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.exagen.com/role/StockOptionPlanStockBasedCompensationExpenseDetails" xlink:type="simple" xlink:href="exdx-20250331.xsd#StockOptionPlanStockBasedCompensationExpenseDetails"/>
  <link:definitionLink xlink:role="http://www.exagen.com/role/StockOptionPlanStockBasedCompensationExpenseDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_ba185eb9-1f64-4d59-a0c7-01631109e263" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_6f732998-ed88-4027-8b16-248e3b12d300" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_ba185eb9-1f64-4d59-a0c7-01631109e263" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_6f732998-ed88-4027-8b16-248e3b12d300" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationAxis_2ef7f2e5-06a5-4476-bb06-cf93d6e322f1" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeStatementLocationAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_6f732998-ed88-4027-8b16-248e3b12d300" xlink:to="loc_us-gaap_IncomeStatementLocationAxis_2ef7f2e5-06a5-4476-bb06-cf93d6e322f1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_2ef7f2e5-06a5-4476-bb06-cf93d6e322f1_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_2ef7f2e5-06a5-4476-bb06-cf93d6e322f1" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_2ef7f2e5-06a5-4476-bb06-cf93d6e322f1_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_6700dbbc-0942-4340-a869-b5aad01d0ee1" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_2ef7f2e5-06a5-4476-bb06-cf93d6e322f1" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_6700dbbc-0942-4340-a869-b5aad01d0ee1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostOfSalesMember_005362b3-a5cf-4b25-a16b-8e1e2c700d67" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CostOfSalesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_6700dbbc-0942-4340-a869-b5aad01d0ee1" xlink:to="loc_us-gaap_CostOfSalesMember_005362b3-a5cf-4b25-a16b-8e1e2c700d67" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SellingGeneralAndAdministrativeExpensesMember_dcd9ad01-af0e-4446-9395-295a8780ea23" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SellingGeneralAndAdministrativeExpensesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_6700dbbc-0942-4340-a869-b5aad01d0ee1" xlink:to="loc_us-gaap_SellingGeneralAndAdministrativeExpensesMember_dcd9ad01-af0e-4446-9395-295a8780ea23" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpenseMember_9fc0bf6f-7689-4a2a-a960-82914926bd35" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ResearchAndDevelopmentExpenseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_6700dbbc-0942-4340-a869-b5aad01d0ee1" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpenseMember_9fc0bf6f-7689-4a2a-a960-82914926bd35" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllocatedShareBasedCompensationExpense_2e204c8d-f10c-4e18-a5ff-457f5292d7fc" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AllocatedShareBasedCompensationExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_ba185eb9-1f64-4d59-a0c7-01631109e263" xlink:to="loc_us-gaap_AllocatedShareBasedCompensationExpense_2e204c8d-f10c-4e18-a5ff-457f5292d7fc" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.exagen.com/role/SegmentReportingNarrativeDetails" xlink:type="simple" xlink:href="exdx-20250331.xsd#SegmentReportingNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.exagen.com/role/SegmentReportingNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentReportingInformationLineItems_08a2985f-ee3b-4206-a43d-22dbc50ec532" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SegmentReportingInformationLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_8c178227-9cd5-44cd-bcd7-eb784e04c55c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_08a2985f-ee3b-4206-a43d-22dbc50ec532" xlink:to="loc_us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_8c178227-9cd5-44cd-bcd7-eb784e04c55c" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementBusinessSegmentsAxis_9d428a85-2b02-4da8-88a2-fe0740bb096b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StatementBusinessSegmentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_8c178227-9cd5-44cd-bcd7-eb784e04c55c" xlink:to="loc_us-gaap_StatementBusinessSegmentsAxis_9d428a85-2b02-4da8-88a2-fe0740bb096b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentDomain_9d428a85-2b02-4da8-88a2-fe0740bb096b_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SegmentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementBusinessSegmentsAxis_9d428a85-2b02-4da8-88a2-fe0740bb096b" xlink:to="loc_us-gaap_SegmentDomain_9d428a85-2b02-4da8-88a2-fe0740bb096b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentDomain_60db70df-f460-478f-a6ba-75a3158e66c2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SegmentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementBusinessSegmentsAxis_9d428a85-2b02-4da8-88a2-fe0740bb096b" xlink:to="loc_us-gaap_SegmentDomain_60db70df-f460-478f-a6ba-75a3158e66c2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_ReportableSegmentMember_e287dac5-b1ac-458b-9ac5-6743fff8c59d" xlink:href="exdx-20250331.xsd#exdx_ReportableSegmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentDomain_60db70df-f460-478f-a6ba-75a3158e66c2" xlink:to="loc_exdx_ReportableSegmentMember_e287dac5-b1ac-458b-9ac5-6743fff8c59d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NumberOfOperatingSegments_b691fbd2-c4a6-49a5-9df3-8e6909202234" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NumberOfOperatingSegments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_08a2985f-ee3b-4206-a43d-22dbc50ec532" xlink:to="loc_us-gaap_NumberOfOperatingSegments_b691fbd2-c4a6-49a5-9df3-8e6909202234" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Assets_4be7bb78-36db-45f6-a28d-7999fc26955d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_Assets"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_08a2985f-ee3b-4206-a43d-22dbc50ec532" xlink:to="loc_us-gaap_Assets_4be7bb78-36db-45f6-a28d-7999fc26955d" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.exagen.com/role/SegmentReportingSegmentRevenueandNetLossDetails" xlink:type="simple" xlink:href="exdx-20250331.xsd#SegmentReportingSegmentRevenueandNetLossDetails"/>
  <link:definitionLink xlink:role="http://www.exagen.com/role/SegmentReportingSegmentRevenueandNetLossDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentReportingInformationLineItems_e57ecd0e-95ca-4ef5-9072-335e08c1a868" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SegmentReportingInformationLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_c3e356ea-4814-4f91-b36c-7f4cd3b31fc7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_e57ecd0e-95ca-4ef5-9072-335e08c1a868" xlink:to="loc_us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_c3e356ea-4814-4f91-b36c-7f4cd3b31fc7" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementBusinessSegmentsAxis_94301eea-2136-4ce3-9e61-e6d2bc3f584a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StatementBusinessSegmentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_c3e356ea-4814-4f91-b36c-7f4cd3b31fc7" xlink:to="loc_us-gaap_StatementBusinessSegmentsAxis_94301eea-2136-4ce3-9e61-e6d2bc3f584a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentDomain_94301eea-2136-4ce3-9e61-e6d2bc3f584a_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SegmentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementBusinessSegmentsAxis_94301eea-2136-4ce3-9e61-e6d2bc3f584a" xlink:to="loc_us-gaap_SegmentDomain_94301eea-2136-4ce3-9e61-e6d2bc3f584a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentDomain_80fbbf0c-a634-4d56-b77c-e340ed831e09" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SegmentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementBusinessSegmentsAxis_94301eea-2136-4ce3-9e61-e6d2bc3f584a" xlink:to="loc_us-gaap_SegmentDomain_80fbbf0c-a634-4d56-b77c-e340ed831e09" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_ReportableSegmentMember_9b3482ae-8e69-4d66-896c-733d48cfb847" xlink:href="exdx-20250331.xsd#exdx_ReportableSegmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentDomain_80fbbf0c-a634-4d56-b77c-e340ed831e09" xlink:to="loc_exdx_ReportableSegmentMember_9b3482ae-8e69-4d66-896c-733d48cfb847" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_0d44b87c-2d90-49c5-b675-e5160fabbff1" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_e57ecd0e-95ca-4ef5-9072-335e08c1a868" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_0d44b87c-2d90-49c5-b675-e5160fabbff1" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostOfGoodsAndServicesSold_49ab3574-b401-4602-8b77-b026df007f91" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CostOfGoodsAndServicesSold"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_e57ecd0e-95ca-4ef5-9072-335e08c1a868" xlink:to="loc_us-gaap_CostOfGoodsAndServicesSold_49ab3574-b401-4602-8b77-b026df007f91" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GrossProfit_98dff059-0597-4eb5-8a5f-9b1fb3c0fe02" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_GrossProfit"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_e57ecd0e-95ca-4ef5-9072-335e08c1a868" xlink:to="loc_us-gaap_GrossProfit_98dff059-0597-4eb5-8a5f-9b1fb3c0fe02" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LaborAndRelatedExpense_5e770cd6-8ddd-48b5-9708-1147f3463024" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LaborAndRelatedExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_e57ecd0e-95ca-4ef5-9072-335e08c1a868" xlink:to="loc_us-gaap_LaborAndRelatedExpense_5e770cd6-8ddd-48b5-9708-1147f3463024" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_OutsideServicesExpense_ad1dec99-ae99-4137-a6e7-eb4fc2dfda20" xlink:href="exdx-20250331.xsd#exdx_OutsideServicesExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_e57ecd0e-95ca-4ef5-9072-335e08c1a868" xlink:to="loc_exdx_OutsideServicesExpense_ad1dec99-ae99-4137-a6e7-eb4fc2dfda20" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OccupancyNet_16cf68e5-8a41-4e87-958e-4faf9a1cf813" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OccupancyNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_e57ecd0e-95ca-4ef5-9072-335e08c1a868" xlink:to="loc_us-gaap_OccupancyNet_16cf68e5-8a41-4e87-958e-4faf9a1cf813" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TravelAndEntertainmentExpense_ef0c93f9-4fea-47c4-884c-784c8b089a11" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_TravelAndEntertainmentExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_e57ecd0e-95ca-4ef5-9072-335e08c1a868" xlink:to="loc_us-gaap_TravelAndEntertainmentExpense_ef0c93f9-4fea-47c4-884c-784c8b089a11" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllocatedShareBasedCompensationExpense_733fc66b-8029-4d49-b62b-6f2d517bcd4a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AllocatedShareBasedCompensationExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_e57ecd0e-95ca-4ef5-9072-335e08c1a868" xlink:to="loc_us-gaap_AllocatedShareBasedCompensationExpense_733fc66b-8029-4d49-b62b-6f2d517bcd4a" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DepreciationDepletionAndAmortization_8b9ab6fc-9e0b-43ca-93b8-ba5a7e6b9ef9" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DepreciationDepletionAndAmortization"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_e57ecd0e-95ca-4ef5-9072-335e08c1a868" xlink:to="loc_us-gaap_DepreciationDepletionAndAmortization_8b9ab6fc-9e0b-43ca-93b8-ba5a7e6b9ef9" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentReportingOtherItemAmount_3f6c7560-69fb-46e0-ab54-13d1a3686443" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SegmentReportingOtherItemAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_e57ecd0e-95ca-4ef5-9072-335e08c1a868" xlink:to="loc_us-gaap_SegmentReportingOtherItemAmount_3f6c7560-69fb-46e0-ab54-13d1a3686443" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingExpenses_e2dea917-55b2-4b59-b612-cb28f27f1bc3" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingExpenses"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_e57ecd0e-95ca-4ef5-9072-335e08c1a868" xlink:to="loc_us-gaap_OperatingExpenses_e2dea917-55b2-4b59-b612-cb28f27f1bc3" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingIncomeLoss_5e97de12-3403-424f-84e3-2400d5320a7d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_e57ecd0e-95ca-4ef5-9072-335e08c1a868" xlink:to="loc_us-gaap_OperatingIncomeLoss_5e97de12-3403-424f-84e3-2400d5320a7d" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestExpenseNonoperating_bfcfdcf2-c4cc-4ef0-a347-95d3874ce434" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InterestExpenseNonoperating"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_e57ecd0e-95ca-4ef5-9072-335e08c1a868" xlink:to="loc_us-gaap_InterestExpenseNonoperating_bfcfdcf2-c4cc-4ef0-a347-95d3874ce434" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentIncomeInterest_4ca4474b-f88d-4c99-9b81-6586aca602e5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InvestmentIncomeInterest"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_e57ecd0e-95ca-4ef5-9072-335e08c1a868" xlink:to="loc_us-gaap_InvestmentIncomeInterest_4ca4474b-f88d-4c99-9b81-6586aca602e5" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_6b055543-110a-418e-bb5e-50e0721087ec" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_e57ecd0e-95ca-4ef5-9072-335e08c1a868" xlink:to="loc_us-gaap_NetIncomeLoss_6b055543-110a-418e-bb5e-50e0721087ec" xlink:type="arc" order="14"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.exagen.com/role/SubsequentEventsDetails" xlink:type="simple" xlink:href="exdx-20250331.xsd#SubsequentEventsDetails"/>
  <link:definitionLink xlink:role="http://www.exagen.com/role/SubsequentEventsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventLineItems_4cb73cdc-b6b9-49fe-9ce1-b843ffddc280" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SubsequentEventLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTable_f0950a61-0772-490f-829d-92ab0202eb62" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SubsequentEventTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_SubsequentEventLineItems_4cb73cdc-b6b9-49fe-9ce1-b843ffddc280" xlink:to="loc_us-gaap_SubsequentEventTable_f0950a61-0772-490f-829d-92ab0202eb62" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityAxis_2e47818f-820b-44a1-bad8-2f8d2750170a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CreditFacilityAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsequentEventTable_f0950a61-0772-490f-829d-92ab0202eb62" xlink:to="loc_us-gaap_CreditFacilityAxis_2e47818f-820b-44a1-bad8-2f8d2750170a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityDomain_2e47818f-820b-44a1-bad8-2f8d2750170a_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CreditFacilityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_CreditFacilityAxis_2e47818f-820b-44a1-bad8-2f8d2750170a" xlink:to="loc_us-gaap_CreditFacilityDomain_2e47818f-820b-44a1-bad8-2f8d2750170a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityDomain_e092c2dc-125b-4dca-8052-1ab42adc087d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CreditFacilityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_CreditFacilityAxis_2e47818f-820b-44a1-bad8-2f8d2750170a" xlink:to="loc_us-gaap_CreditFacilityDomain_e092c2dc-125b-4dca-8052-1ab42adc087d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DelayedDrawTermLoanMember_5a98735b-f065-4c55-99f1-b7692b9e8469" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DelayedDrawTermLoanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CreditFacilityDomain_e092c2dc-125b-4dca-8052-1ab42adc087d" xlink:to="loc_us-gaap_DelayedDrawTermLoanMember_5a98735b-f065-4c55-99f1-b7692b9e8469" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentAxis_03470cc6-486c-407f-9f5e-91796421f33e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsequentEventTable_f0950a61-0772-490f-829d-92ab0202eb62" xlink:to="loc_us-gaap_DebtInstrumentAxis_03470cc6-486c-407f-9f5e-91796421f33e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_03470cc6-486c-407f-9f5e-91796421f33e_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DebtInstrumentAxis_03470cc6-486c-407f-9f5e-91796421f33e" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_03470cc6-486c-407f-9f5e-91796421f33e_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_c90697f1-454f-4fdb-ac6d-8b1a4266bf7a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DebtInstrumentAxis_03470cc6-486c-407f-9f5e-91796421f33e" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_c90697f1-454f-4fdb-ac6d-8b1a4266bf7a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_PerceptiveTermLoanFacilityMember_e0c9aaab-a992-4316-88d0-ecb60dac9dbb" xlink:href="exdx-20250331.xsd#exdx_PerceptiveTermLoanFacilityMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_c90697f1-454f-4fdb-ac6d-8b1a4266bf7a" xlink:to="loc_exdx_PerceptiveTermLoanFacilityMember_e0c9aaab-a992-4316-88d0-ecb60dac9dbb" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_PerceptiveTermLoanFacilityTrancheALoanMember_c8d84227-29b8-4541-bb13-eb4bc4cda905" xlink:href="exdx-20250331.xsd#exdx_PerceptiveTermLoanFacilityTrancheALoanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_c90697f1-454f-4fdb-ac6d-8b1a4266bf7a" xlink:to="loc_exdx_PerceptiveTermLoanFacilityTrancheALoanMember_c8d84227-29b8-4541-bb13-eb4bc4cda905" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_PerceptiveTermLoanFacilityTrancheBLoanMember_063de45c-d67a-42f8-922e-9385e07f2817" xlink:href="exdx-20250331.xsd#exdx_PerceptiveTermLoanFacilityTrancheBLoanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_c90697f1-454f-4fdb-ac6d-8b1a4266bf7a" xlink:to="loc_exdx_PerceptiveTermLoanFacilityTrancheBLoanMember_063de45c-d67a-42f8-922e-9385e07f2817" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_PerceptiveTermLoanFacilityTrancheCLoanMember_a6b33447-4a82-4401-87ed-78a48d2e468e" xlink:href="exdx-20250331.xsd#exdx_PerceptiveTermLoanFacilityTrancheCLoanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_c90697f1-454f-4fdb-ac6d-8b1a4266bf7a" xlink:to="loc_exdx_PerceptiveTermLoanFacilityTrancheCLoanMember_a6b33447-4a82-4401-87ed-78a48d2e468e" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_PerceptiveTermLoanFacilityTrancheDLoanMember_6b86ab39-0f67-485e-9908-86370a287ecf" xlink:href="exdx-20250331.xsd#exdx_PerceptiveTermLoanFacilityTrancheDLoanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_c90697f1-454f-4fdb-ac6d-8b1a4266bf7a" xlink:to="loc_exdx_PerceptiveTermLoanFacilityTrancheDLoanMember_6b86ab39-0f67-485e-9908-86370a287ecf" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityAxis_3af45513-c43a-4d13-9340-60246e8c30a5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LineOfCreditFacilityAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsequentEventTable_f0950a61-0772-490f-829d-92ab0202eb62" xlink:to="loc_us-gaap_LineOfCreditFacilityAxis_3af45513-c43a-4d13-9340-60246e8c30a5" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityLenderDomain_3af45513-c43a-4d13-9340-60246e8c30a5_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LineOfCreditFacilityLenderDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_LineOfCreditFacilityAxis_3af45513-c43a-4d13-9340-60246e8c30a5" xlink:to="loc_us-gaap_LineOfCreditFacilityLenderDomain_3af45513-c43a-4d13-9340-60246e8c30a5_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityLenderDomain_0a7a1cf3-42ab-430d-a8d1-f6cb65e1315e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LineOfCreditFacilityLenderDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_LineOfCreditFacilityAxis_3af45513-c43a-4d13-9340-60246e8c30a5" xlink:to="loc_us-gaap_LineOfCreditFacilityLenderDomain_0a7a1cf3-42ab-430d-a8d1-f6cb65e1315e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_PerceptiveCreditHoldingsIVLPMember_1d2ede51-a661-4372-92c1-8a38d4c03727" xlink:href="exdx-20250331.xsd#exdx_PerceptiveCreditHoldingsIVLPMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLenderDomain_0a7a1cf3-42ab-430d-a8d1-f6cb65e1315e" xlink:to="loc_exdx_PerceptiveCreditHoldingsIVLPMember_1d2ede51-a661-4372-92c1-8a38d4c03727" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeAxis_a9308b90-ef15-4ba1-9cc4-69a23a17ad8a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SubsequentEventTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsequentEventTable_f0950a61-0772-490f-829d-92ab0202eb62" xlink:to="loc_us-gaap_SubsequentEventTypeAxis_a9308b90-ef15-4ba1-9cc4-69a23a17ad8a" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeDomain_a9308b90-ef15-4ba1-9cc4-69a23a17ad8a_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SubsequentEventTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_SubsequentEventTypeAxis_a9308b90-ef15-4ba1-9cc4-69a23a17ad8a" xlink:to="loc_us-gaap_SubsequentEventTypeDomain_a9308b90-ef15-4ba1-9cc4-69a23a17ad8a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeDomain_66e10d2f-6f18-416e-b71c-bfd90050efb9" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SubsequentEventTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_SubsequentEventTypeAxis_a9308b90-ef15-4ba1-9cc4-69a23a17ad8a" xlink:to="loc_us-gaap_SubsequentEventTypeDomain_66e10d2f-6f18-416e-b71c-bfd90050efb9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventMember_fafe5e8f-0dfe-4f16-8a23-6948d21a7d7d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SubsequentEventMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventTypeDomain_66e10d2f-6f18-416e-b71c-bfd90050efb9" xlink:to="loc_us-gaap_SubsequentEventMember_fafe5e8f-0dfe-4f16-8a23-6948d21a7d7d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_ab56ce2e-42c1-4316-bd55-726267258f73" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsequentEventTable_f0950a61-0772-490f-829d-92ab0202eb62" xlink:to="loc_srt_RangeAxis_ab56ce2e-42c1-4316-bd55-726267258f73" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_ab56ce2e-42c1-4316-bd55-726267258f73_default" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_ab56ce2e-42c1-4316-bd55-726267258f73" xlink:to="loc_srt_RangeMember_ab56ce2e-42c1-4316-bd55-726267258f73_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_2cdedfb2-937e-404c-833f-bf51b64d1901" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_ab56ce2e-42c1-4316-bd55-726267258f73" xlink:to="loc_srt_RangeMember_2cdedfb2-937e-404c-833f-bf51b64d1901" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_0bb86daf-24b2-438d-8a95-2ed4034cf5f0" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_MinimumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_2cdedfb2-937e-404c-833f-bf51b64d1901" xlink:to="loc_srt_MinimumMember_0bb86daf-24b2-438d-8a95-2ed4034cf5f0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_556b519e-6e8b-40af-905d-1c9965dd3152" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_2cdedfb2-937e-404c-833f-bf51b64d1901" xlink:to="loc_srt_MaximumMember_556b519e-6e8b-40af-905d-1c9965dd3152" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightAxis_70b507e2-3148-4505-81e5-d857fdbce97c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ClassOfWarrantOrRightAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsequentEventTable_f0950a61-0772-490f-829d-92ab0202eb62" xlink:to="loc_us-gaap_ClassOfWarrantOrRightAxis_70b507e2-3148-4505-81e5-d857fdbce97c" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightDomain_70b507e2-3148-4505-81e5-d857fdbce97c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ClassOfWarrantOrRightDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ClassOfWarrantOrRightAxis_70b507e2-3148-4505-81e5-d857fdbce97c" xlink:to="loc_us-gaap_ClassOfWarrantOrRightDomain_70b507e2-3148-4505-81e5-d857fdbce97c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightDomain_93fc127f-b426-49bd-bfe1-371524cd98e4" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ClassOfWarrantOrRightDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ClassOfWarrantOrRightAxis_70b507e2-3148-4505-81e5-d857fdbce97c" xlink:to="loc_us-gaap_ClassOfWarrantOrRightDomain_93fc127f-b426-49bd-bfe1-371524cd98e4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_CreditAgreementWarrantsMember_f771f347-a4b4-4729-8b09-f9623c418a38" xlink:href="exdx-20250331.xsd#exdx_CreditAgreementWarrantsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightDomain_93fc127f-b426-49bd-bfe1-371524cd98e4" xlink:to="loc_exdx_CreditAgreementWarrantsMember_f771f347-a4b4-4729-8b09-f9623c418a38" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_CreditAgreementWarrantsTrancheAMember_5fe649fa-a97c-48f6-bb2e-80df93d23bc2" xlink:href="exdx-20250331.xsd#exdx_CreditAgreementWarrantsTrancheAMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightDomain_93fc127f-b426-49bd-bfe1-371524cd98e4" xlink:to="loc_exdx_CreditAgreementWarrantsTrancheAMember_5fe649fa-a97c-48f6-bb2e-80df93d23bc2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_CreditAgreementWarrantsTrancheBMember_fabe2979-0e16-4941-a726-b4382fdfb022" xlink:href="exdx-20250331.xsd#exdx_CreditAgreementWarrantsTrancheBMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightDomain_93fc127f-b426-49bd-bfe1-371524cd98e4" xlink:to="loc_exdx_CreditAgreementWarrantsTrancheBMember_fabe2979-0e16-4941-a726-b4382fdfb022" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_CreditAgreementWarrantsTrancheCMember_4b0840b9-4a95-48fc-bac8-100a47114bac" xlink:href="exdx-20250331.xsd#exdx_CreditAgreementWarrantsTrancheCMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightDomain_93fc127f-b426-49bd-bfe1-371524cd98e4" xlink:to="loc_exdx_CreditAgreementWarrantsTrancheCMember_4b0840b9-4a95-48fc-bac8-100a47114bac" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_CreditAgreementWarrantsTrancheDMember_47488cf4-52c9-4909-9ff3-5b4048ec723e" xlink:href="exdx-20250331.xsd#exdx_CreditAgreementWarrantsTrancheDMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightDomain_93fc127f-b426-49bd-bfe1-371524cd98e4" xlink:to="loc_exdx_CreditAgreementWarrantsTrancheDMember_47488cf4-52c9-4909-9ff3-5b4048ec723e" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity_6d500cfa-9b5d-4174-b6bd-087044910c33" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_4cb73cdc-b6b9-49fe-9ce1-b843ffddc280" xlink:to="loc_us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity_6d500cfa-9b5d-4174-b6bd-087044910c33" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromLongTermLinesOfCredit_d25d5dd5-f107-423c-ad0e-598832fbd45d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ProceedsFromLongTermLinesOfCredit"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_4cb73cdc-b6b9-49fe-9ce1-b843ffddc280" xlink:to="loc_us-gaap_ProceedsFromLongTermLinesOfCredit_d25d5dd5-f107-423c-ad0e-598832fbd45d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_LineOfCreditFacilityAccordionFeatureIncreaseLimit_64eacc02-c7bb-4586-bfcc-dba719c38e02" xlink:href="exdx-20250331.xsd#exdx_LineOfCreditFacilityAccordionFeatureIncreaseLimit"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_4cb73cdc-b6b9-49fe-9ce1-b843ffddc280" xlink:to="loc_exdx_LineOfCreditFacilityAccordionFeatureIncreaseLimit_64eacc02-c7bb-4586-bfcc-dba719c38e02" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentVariableInterestRateTypeExtensibleEnumeration_442b261c-0f19-4fc4-b310-073ae056de14" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentVariableInterestRateTypeExtensibleEnumeration"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_4cb73cdc-b6b9-49fe-9ce1-b843ffddc280" xlink:to="loc_us-gaap_DebtInstrumentVariableInterestRateTypeExtensibleEnumeration_442b261c-0f19-4fc4-b310-073ae056de14" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentInterestRateStatedPercentage_5be47982-eef9-4540-afae-014c2650531e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentInterestRateStatedPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_4cb73cdc-b6b9-49fe-9ce1-b843ffddc280" xlink:to="loc_us-gaap_DebtInstrumentInterestRateStatedPercentage_5be47982-eef9-4540-afae-014c2650531e" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentBasisSpreadOnVariableRate1_ae62fda2-6baf-4712-a1ab-e88365955d89" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentBasisSpreadOnVariableRate1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_4cb73cdc-b6b9-49fe-9ce1-b843ffddc280" xlink:to="loc_us-gaap_DebtInstrumentBasisSpreadOnVariableRate1_ae62fda2-6baf-4712-a1ab-e88365955d89" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentInterestRateIncreaseDecrease_ffe09f3e-38df-405d-afe8-b6623f088a70" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentInterestRateIncreaseDecrease"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_4cb73cdc-b6b9-49fe-9ce1-b843ffddc280" xlink:to="loc_us-gaap_DebtInstrumentInterestRateIncreaseDecrease_ffe09f3e-38df-405d-afe8-b6623f088a70" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_DebtInstrumentInterestRateDebtPrepaymentPercentage_b4286b50-6b4e-4ad7-b94e-0a5677147404" xlink:href="exdx-20250331.xsd#exdx_DebtInstrumentInterestRateDebtPrepaymentPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_4cb73cdc-b6b9-49fe-9ce1-b843ffddc280" xlink:to="loc_exdx_DebtInstrumentInterestRateDebtPrepaymentPercentage_b4286b50-6b4e-4ad7-b94e-0a5677147404" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByWarrantsOrRights_a224eeab-c444-49b2-bc34-c6e53fc14672" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByWarrantsOrRights"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_4cb73cdc-b6b9-49fe-9ce1-b843ffddc280" xlink:to="loc_us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByWarrantsOrRights_a224eeab-c444-49b2-bc34-c6e53fc14672" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WarrantsAndRightsOutstandingTerm_5922e6a8-9a15-485b-b3e9-58768621a14e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_WarrantsAndRightsOutstandingTerm"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_4cb73cdc-b6b9-49fe-9ce1-b843ffddc280" xlink:to="loc_us-gaap_WarrantsAndRightsOutstandingTerm_5922e6a8-9a15-485b-b3e9-58768621a14e" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_LineOfCreditFacilityCovenantMinimumUnrestrictedCashBalance_07a5f41a-e3e4-4b59-a25e-0d2cce052320" xlink:href="exdx-20250331.xsd#exdx_LineOfCreditFacilityCovenantMinimumUnrestrictedCashBalance"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_4cb73cdc-b6b9-49fe-9ce1-b843ffddc280" xlink:to="loc_exdx_LineOfCreditFacilityCovenantMinimumUnrestrictedCashBalance_07a5f41a-e3e4-4b59-a25e-0d2cce052320" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_ClassOfWarrantOrRightVestedAndExercisable_f32c7f4c-29d9-45f4-8984-0a5c3ba91166" xlink:href="exdx-20250331.xsd#exdx_ClassOfWarrantOrRightVestedAndExercisable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_4cb73cdc-b6b9-49fe-9ce1-b843ffddc280" xlink:to="loc_exdx_ClassOfWarrantOrRightVestedAndExercisable_f32c7f4c-29d9-45f4-8984-0a5c3ba91166" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_ClassOfWarrantOrRightContingentVestedAndExercisable_d9156d07-ea46-43c8-9042-b930d016fbbd" xlink:href="exdx-20250331.xsd#exdx_ClassOfWarrantOrRightContingentVestedAndExercisable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_4cb73cdc-b6b9-49fe-9ce1-b843ffddc280" xlink:to="loc_exdx_ClassOfWarrantOrRightContingentVestedAndExercisable_d9156d07-ea46-43c8-9042-b930d016fbbd" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_ClassOfWarrantOrRightSecuritiesCalledByWarrantsOrRightsPercentage_65497d72-10d2-49f3-8dff-8b4d21e9eec3" xlink:href="exdx-20250331.xsd#exdx_ClassOfWarrantOrRightSecuritiesCalledByWarrantsOrRightsPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_4cb73cdc-b6b9-49fe-9ce1-b843ffddc280" xlink:to="loc_exdx_ClassOfWarrantOrRightSecuritiesCalledByWarrantsOrRightsPercentage_65497d72-10d2-49f3-8dff-8b4d21e9eec3" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1_c3f57abf-cf2d-4ca4-baa1-055e1becb77b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_4cb73cdc-b6b9-49fe-9ce1-b843ffddc280" xlink:to="loc_us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1_c3f57abf-cf2d-4ca4-baa1-055e1becb77b" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRightsRemainingBalance_4f161037-55d8-4f25-b32f-9037add57efe" xlink:href="exdx-20250331.xsd#exdx_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRightsRemainingBalance"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_4cb73cdc-b6b9-49fe-9ce1-b843ffddc280" xlink:to="loc_exdx_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRightsRemainingBalance_4f161037-55d8-4f25-b32f-9037add57efe" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_WarrantIssuedToPurchaseOnCommonStockBusinessDays_57b3d8ac-6212-49bd-8eb2-03405da1233b" xlink:href="exdx-20250331.xsd#exdx_WarrantIssuedToPurchaseOnCommonStockBusinessDays"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_4cb73cdc-b6b9-49fe-9ce1-b843ffddc280" xlink:to="loc_exdx_WarrantIssuedToPurchaseOnCommonStockBusinessDays_57b3d8ac-6212-49bd-8eb2-03405da1233b" xlink:type="arc" order="16"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_WarrantIssuedToPurchaseOnCommonStockPercentage_023ae94d-d0f9-4344-b25a-1951c7850015" xlink:href="exdx-20250331.xsd#exdx_WarrantIssuedToPurchaseOnCommonStockPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_4cb73cdc-b6b9-49fe-9ce1-b843ffddc280" xlink:to="loc_exdx_WarrantIssuedToPurchaseOnCommonStockPercentage_023ae94d-d0f9-4344-b25a-1951c7850015" xlink:type="arc" order="17"/>
  </link:definitionLink>
</link:linkbase>
