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

<!--XBRL Document Created with Wdesk from Workiva-->
<!--Copyright 2023 Workiva-->
<!--r:986b824d-5d9a-48e8-aa5f-764c09336517,g:f595c211-a573-4e45-813e-7a98f9aeca2c-->
<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" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd">
  <link:roleRef roleURI="http://www.exagen.com/role/UnauditedCondensedBalanceSheets" xlink:type="simple" xlink:href="exdx-20230331.xsd#UnauditedCondensedBalanceSheets"/>
  <link:calculationLink xlink:role="http://www.exagen.com/role/UnauditedCondensedBalanceSheets" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesAndStockholdersEquity_5da1da0a-4256-4cfb-8fba-21fd081da241" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LiabilitiesAndStockholdersEquity"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_afeae530-5fd1-4ed1-9767-a03fc05391dd" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StockholdersEquity"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquity_5da1da0a-4256-4cfb-8fba-21fd081da241" xlink:to="loc_us-gaap_StockholdersEquity_afeae530-5fd1-4ed1-9767-a03fc05391dd" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Liabilities_d11c585d-0ded-4ed2-b7f3-d984d247e781" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_Liabilities"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquity_5da1da0a-4256-4cfb-8fba-21fd081da241" xlink:to="loc_us-gaap_Liabilities_d11c585d-0ded-4ed2-b7f3-d984d247e781" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommitmentsAndContingencies_2de3e329-abc1-4fef-a5f5-f087efce7e7c" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CommitmentsAndContingencies"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquity_5da1da0a-4256-4cfb-8fba-21fd081da241" xlink:to="loc_us-gaap_CommitmentsAndContingencies_2de3e329-abc1-4fef-a5f5-f087efce7e7c" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Assets_34403448-f14e-4344-b41e-da0e73a5673b" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_Assets"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherAssetsNoncurrent_ed31eba2-6d6f-45e4-aaaf-69b0a0f9c133" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OtherAssetsNoncurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_34403448-f14e-4344-b41e-da0e73a5673b" xlink:to="loc_us-gaap_OtherAssetsNoncurrent_ed31eba2-6d6f-45e4-aaaf-69b0a0f9c133" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentAndFinanceLeaseRightOfUseAssetAfterAccumulatedDepreciationAndAmortization_7e0c1dbd-a5c1-4518-a234-69714bdac82f" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PropertyPlantAndEquipmentAndFinanceLeaseRightOfUseAssetAfterAccumulatedDepreciationAndAmortization"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_34403448-f14e-4344-b41e-da0e73a5673b" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentAndFinanceLeaseRightOfUseAssetAfterAccumulatedDepreciationAndAmortization_7e0c1dbd-a5c1-4518-a234-69714bdac82f" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsCurrent_e2413f6c-661a-4c3a-8353-36045e063368" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AssetsCurrent"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_34403448-f14e-4344-b41e-da0e73a5673b" xlink:to="loc_us-gaap_AssetsCurrent_e2413f6c-661a-4c3a-8353-36045e063368" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseRightOfUseAsset_f331cd3c-e4da-4caf-afe8-c70153db6472" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OperatingLeaseRightOfUseAsset"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_34403448-f14e-4344-b41e-da0e73a5673b" xlink:to="loc_us-gaap_OperatingLeaseRightOfUseAsset_f331cd3c-e4da-4caf-afe8-c70153db6472" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesCurrent_d9e104df-978d-4c78-806f-9b1868827fd2" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LiabilitiesCurrent"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebtCurrent_c1e50210-e312-469c-895a-1e68ecdd61eb" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongTermDebtCurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_d9e104df-978d-4c78-806f-9b1868827fd2" xlink:to="loc_us-gaap_LongTermDebtCurrent_c1e50210-e312-469c-895a-1e68ecdd61eb" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsPayableCurrent_640ef123-9cbf-449f-b330-d1cd5f8d3c0f" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AccountsPayableCurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_d9e104df-978d-4c78-806f-9b1868827fd2" xlink:to="loc_us-gaap_AccountsPayableCurrent_640ef123-9cbf-449f-b330-d1cd5f8d3c0f" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccruedLiabilitiesCurrent_aa52a7b5-9f35-4673-b25c-8228bd93e5c8" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AccruedLiabilitiesCurrent"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_d9e104df-978d-4c78-806f-9b1868827fd2" xlink:to="loc_us-gaap_AccruedLiabilitiesCurrent_aa52a7b5-9f35-4673-b25c-8228bd93e5c8" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiabilityCurrent_081e4e43-c92b-43d8-8ba9-7c85ffc096f7" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OperatingLeaseLiabilityCurrent"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_d9e104df-978d-4c78-806f-9b1868827fd2" xlink:to="loc_us-gaap_OperatingLeaseLiabilityCurrent_081e4e43-c92b-43d8-8ba9-7c85ffc096f7" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Liabilities_17dcf0a5-479e-46eb-b03c-799038b63fa3" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_Liabilities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebtNoncurrent_bf7831ae-3748-46d4-88ef-95b745e7d24d" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongTermDebtNoncurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_17dcf0a5-479e-46eb-b03c-799038b63fa3" xlink:to="loc_us-gaap_LongTermDebtNoncurrent_bf7831ae-3748-46d4-88ef-95b745e7d24d" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiabilityNoncurrent_628d0ad6-7e5f-48db-923b-0c8175479ff5" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OperatingLeaseLiabilityNoncurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_17dcf0a5-479e-46eb-b03c-799038b63fa3" xlink:to="loc_us-gaap_OperatingLeaseLiabilityNoncurrent_628d0ad6-7e5f-48db-923b-0c8175479ff5" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherLiabilitiesNoncurrent_59de1c63-69df-4565-8d46-7a62fbf1b0b7" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OtherLiabilitiesNoncurrent"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_17dcf0a5-479e-46eb-b03c-799038b63fa3" xlink:to="loc_us-gaap_OtherLiabilitiesNoncurrent_59de1c63-69df-4565-8d46-7a62fbf1b0b7" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesCurrent_1c1c5c83-bab9-4c85-a86d-d59b4c30d7a5" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LiabilitiesCurrent"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_17dcf0a5-479e-46eb-b03c-799038b63fa3" xlink:to="loc_us-gaap_LiabilitiesCurrent_1c1c5c83-bab9-4c85-a86d-d59b4c30d7a5" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsCurrent_dbd0256c-51eb-4e9c-86c3-81d5ce03bc9e" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AssetsCurrent"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_302d99b0-6770-450c-80b3-609806b8b766" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_dbd0256c-51eb-4e9c-86c3-81d5ce03bc9e" xlink:to="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_302d99b0-6770-450c-80b3-609806b8b766" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsReceivableNetCurrent_ec05e5f6-bad0-41d0-978f-c7005e57446e" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AccountsReceivableNetCurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_dbd0256c-51eb-4e9c-86c3-81d5ce03bc9e" xlink:to="loc_us-gaap_AccountsReceivableNetCurrent_ec05e5f6-bad0-41d0-978f-c7005e57446e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PrepaidExpenseAndOtherAssets_bc9018e1-783a-4d40-889c-8f71f9e7aebc" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PrepaidExpenseAndOtherAssets"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_dbd0256c-51eb-4e9c-86c3-81d5ce03bc9e" xlink:to="loc_us-gaap_PrepaidExpenseAndOtherAssets_bc9018e1-783a-4d40-889c-8f71f9e7aebc" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_eeaa3b4b-7dc6-4dd5-8c35-a6ef75f09523" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StockholdersEquity"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdditionalPaidInCapital_88adc478-7609-4653-b4fe-e5a301c91df9" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AdditionalPaidInCapital"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_eeaa3b4b-7dc6-4dd5-8c35-a6ef75f09523" xlink:to="loc_us-gaap_AdditionalPaidInCapital_88adc478-7609-4653-b4fe-e5a301c91df9" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockValue_9ac6edfc-8e65-4698-bc71-0ecd8b5810f1" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CommonStockValue"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_eeaa3b4b-7dc6-4dd5-8c35-a6ef75f09523" xlink:to="loc_us-gaap_CommonStockValue_9ac6edfc-8e65-4698-bc71-0ecd8b5810f1" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetainedEarningsAccumulatedDeficit_e1f24a7f-b4fd-4fef-992b-209f7d20238c" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RetainedEarningsAccumulatedDeficit"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_eeaa3b4b-7dc6-4dd5-8c35-a6ef75f09523" xlink:to="loc_us-gaap_RetainedEarningsAccumulatedDeficit_e1f24a7f-b4fd-4fef-992b-209f7d20238c" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockValue_5c1f1fc9-4efe-4c77-a0ba-42acc8a9b7ea" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PreferredStockValue"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_eeaa3b4b-7dc6-4dd5-8c35-a6ef75f09523" xlink:to="loc_us-gaap_PreferredStockValue_5c1f1fc9-4efe-4c77-a0ba-42acc8a9b7ea" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.exagen.com/role/UnauditedCondensedStatementsofOperations" xlink:type="simple" xlink:href="exdx-20230331.xsd#UnauditedCondensedStatementsofOperations"/>
  <link:calculationLink xlink:role="http://www.exagen.com/role/UnauditedCondensedStatementsofOperations" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingIncomeLoss_49cc6d2b-c956-4388-a298-d652728f720d" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OperatingIncomeLoss"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostsAndExpenses_0eca99e9-9cca-4141-8ecf-8f112c24061b" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CostsAndExpenses"/>
    <link:calculationArc order="1" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingIncomeLoss_49cc6d2b-c956-4388-a298-d652728f720d" xlink:to="loc_us-gaap_CostsAndExpenses_0eca99e9-9cca-4141-8ecf-8f112c24061b" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_fe2f0076-41f0-4362-83a8-31c200b43be1" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingIncomeLoss_49cc6d2b-c956-4388-a298-d652728f720d" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_fe2f0076-41f0-4362-83a8-31c200b43be1" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_53afed2e-3577-4f24-b1aa-9b581036c414" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_NetIncomeLoss"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestExpense_ad39bfb1-3d61-472c-bdee-96518b7eb6be" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InterestExpense"/>
    <link:calculationArc order="1" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_53afed2e-3577-4f24-b1aa-9b581036c414" xlink:to="loc_us-gaap_InterestExpense_ad39bfb1-3d61-472c-bdee-96518b7eb6be" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingIncomeLoss_8bb05c3b-12b6-477a-9d99-4c36b04cd7ee" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OperatingIncomeLoss"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_53afed2e-3577-4f24-b1aa-9b581036c414" xlink:to="loc_us-gaap_OperatingIncomeLoss_8bb05c3b-12b6-477a-9d99-4c36b04cd7ee" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestIncomeExpenseNonoperatingNet_5cff18f4-9c44-422e-8964-159e178fa530" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InterestIncomeExpenseNonoperatingNet"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_53afed2e-3577-4f24-b1aa-9b581036c414" xlink:to="loc_us-gaap_InterestIncomeExpenseNonoperatingNet_5cff18f4-9c44-422e-8964-159e178fa530" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostsAndExpenses_f236a544-8cbc-4f6f-bf31-400fc8e9db72" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CostsAndExpenses"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpense_255dc3ce-1774-4cfe-aaa7-6c978d20a2d6" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ResearchAndDevelopmentExpense"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CostsAndExpenses_f236a544-8cbc-4f6f-bf31-400fc8e9db72" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpense_255dc3ce-1774-4cfe-aaa7-6c978d20a2d6" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostOfGoodsAndServicesSold_79dddea5-2081-4ef1-943b-ff926a238bef" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CostOfGoodsAndServicesSold"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CostsAndExpenses_f236a544-8cbc-4f6f-bf31-400fc8e9db72" xlink:to="loc_us-gaap_CostOfGoodsAndServicesSold_79dddea5-2081-4ef1-943b-ff926a238bef" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SellingGeneralAndAdministrativeExpense_6965ae42-ffd5-4750-8637-8d9fee504eb3" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_SellingGeneralAndAdministrativeExpense"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CostsAndExpenses_f236a544-8cbc-4f6f-bf31-400fc8e9db72" xlink:to="loc_us-gaap_SellingGeneralAndAdministrativeExpense_6965ae42-ffd5-4750-8637-8d9fee504eb3" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.exagen.com/role/UnauditedCondensedStatementsofCashFlows" xlink:type="simple" xlink:href="exdx-20230331.xsd#UnauditedCondensedStatementsofCashFlows"/>
  <link:calculationLink xlink:role="http://www.exagen.com/role/UnauditedCondensedStatementsofCashFlows" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_a3b815cf-25df-4a4d-8d57-898e57115ae2" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_44d8b599-5455-4d07-abc6-1076b809c17e" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivities"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_a3b815cf-25df-4a4d-8d57-898e57115ae2" xlink:to="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_44d8b599-5455-4d07-abc6-1076b809c17e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_437ac9d1-3aed-426e-a6e2-0d0fa565d985" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivities"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_a3b815cf-25df-4a4d-8d57-898e57115ae2" xlink:to="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_437ac9d1-3aed-426e-a6e2-0d0fa565d985" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_3ce894e1-353f-4d8b-93c9-b180a1293d5b" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivities"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_a3b815cf-25df-4a4d-8d57-898e57115ae2" xlink:to="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_3ce894e1-353f-4d8b-93c9-b180a1293d5b" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_db5f83aa-0978-40ae-94ea-fb5182c27f48" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivities"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_NonCashLeaseExpense_b16da8dd-c4b1-4b11-84a7-00ad384339e9" xlink:href="exdx-20230331.xsd#exdx_NonCashLeaseExpense"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_db5f83aa-0978-40ae-94ea-fb5182c27f48" xlink:to="loc_exdx_NonCashLeaseExpense_b16da8dd-c4b1-4b11-84a7-00ad384339e9" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaidInKindInterest_2faf0608-f00d-46e3-8cb1-65654d38ae63" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PaidInKindInterest"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_db5f83aa-0978-40ae-94ea-fb5182c27f48" xlink:to="loc_us-gaap_PaidInKindInterest_2faf0608-f00d-46e3-8cb1-65654d38ae63" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInAccountsReceivable_0c584023-07ed-4cb9-9e36-f70f3a1f690f" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_IncreaseDecreaseInAccountsReceivable"/>
    <link:calculationArc order="3" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_db5f83aa-0978-40ae-94ea-fb5182c27f48" xlink:to="loc_us-gaap_IncreaseDecreaseInAccountsReceivable_0c584023-07ed-4cb9-9e36-f70f3a1f690f" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInOperatingLeaseLiability_240d9f13-7765-4c37-8714-6ff907485c78" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_IncreaseDecreaseInOperatingLeaseLiability"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_db5f83aa-0978-40ae-94ea-fb5182c27f48" xlink:to="loc_us-gaap_IncreaseDecreaseInOperatingLeaseLiability_240d9f13-7765-4c37-8714-6ff907485c78" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInAccountsPayable_1e46caf1-1b08-4f7b-8b2c-fa7ed3891c25" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_IncreaseDecreaseInAccountsPayable"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_db5f83aa-0978-40ae-94ea-fb5182c27f48" xlink:to="loc_us-gaap_IncreaseDecreaseInAccountsPayable_1e46caf1-1b08-4f7b-8b2c-fa7ed3891c25" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostOfGoodsAndServicesSoldDepreciationAndAmortization_55c554b3-4e7f-4af9-80b2-cbe1001972ad" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CostOfGoodsAndServicesSoldDepreciationAndAmortization"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_db5f83aa-0978-40ae-94ea-fb5182c27f48" xlink:to="loc_us-gaap_CostOfGoodsAndServicesSoldDepreciationAndAmortization_55c554b3-4e7f-4af9-80b2-cbe1001972ad" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInOtherNoncurrentAssets_5c86bba8-6a05-4360-ab04-022a5a35ce97" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_IncreaseDecreaseInOtherNoncurrentAssets"/>
    <link:calculationArc order="7" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_db5f83aa-0978-40ae-94ea-fb5182c27f48" xlink:to="loc_us-gaap_IncreaseDecreaseInOtherNoncurrentAssets_5c86bba8-6a05-4360-ab04-022a5a35ce97" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_IncreaseDecreaseInPrepaidExpenseAndCurrentOtherAssets_b1fe4b32-0be7-42d5-b59d-a07f75286e9f" xlink:href="exdx-20230331.xsd#exdx_IncreaseDecreaseInPrepaidExpenseAndCurrentOtherAssets"/>
    <link:calculationArc order="8" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_db5f83aa-0978-40ae-94ea-fb5182c27f48" xlink:to="loc_exdx_IncreaseDecreaseInPrepaidExpenseAndCurrentOtherAssets_b1fe4b32-0be7-42d5-b59d-a07f75286e9f" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_d9fd77e0-3177-4805-a57f-d47e392131da" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_NetIncomeLoss"/>
    <link:calculationArc order="9" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_db5f83aa-0978-40ae-94ea-fb5182c27f48" xlink:to="loc_us-gaap_NetIncomeLoss_d9fd77e0-3177-4805-a57f-d47e392131da" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GainLossOnDispositionOfAssets1_45cff85e-081f-4e77-973d-212eb7f5db65" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_GainLossOnDispositionOfAssets1"/>
    <link:calculationArc order="10" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_db5f83aa-0978-40ae-94ea-fb5182c27f48" xlink:to="loc_us-gaap_GainLossOnDispositionOfAssets1_45cff85e-081f-4e77-973d-212eb7f5db65" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInAccruedLiabilitiesAndOtherOperatingLiabilities_acefcadc-b1e6-423d-a9c3-330fdc85ea9b" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_IncreaseDecreaseInAccruedLiabilitiesAndOtherOperatingLiabilities"/>
    <link:calculationArc order="11" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_db5f83aa-0978-40ae-94ea-fb5182c27f48" xlink:to="loc_us-gaap_IncreaseDecreaseInAccruedLiabilitiesAndOtherOperatingLiabilities_acefcadc-b1e6-423d-a9c3-330fdc85ea9b" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensation_7bb89445-6d21-4156-a3c7-c1053a1659a1" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ShareBasedCompensation"/>
    <link:calculationArc order="12" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_db5f83aa-0978-40ae-94ea-fb5182c27f48" xlink:to="loc_us-gaap_ShareBasedCompensation_7bb89445-6d21-4156-a3c7-c1053a1659a1" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AmortizationOfFinancingCostsAndDiscounts_36530f14-9b8d-4573-87bf-806176588a72" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AmortizationOfFinancingCostsAndDiscounts"/>
    <link:calculationArc order="13" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_db5f83aa-0978-40ae-94ea-fb5182c27f48" xlink:to="loc_us-gaap_AmortizationOfFinancingCostsAndDiscounts_36530f14-9b8d-4573-87bf-806176588a72" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_6689d1a3-cc3e-4940-9908-0fa64be6257f" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromStockPlans_d069b20d-94b9-4843-bdd0-98624d551b86" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ProceedsFromStockPlans"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_6689d1a3-cc3e-4940-9908-0fa64be6257f" xlink:to="loc_us-gaap_ProceedsFromStockPlans_d069b20d-94b9-4843-bdd0-98624d551b86" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation_081bb523-769b-44ac-8416-a1e08308a872" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_6689d1a3-cc3e-4940-9908-0fa64be6257f" xlink:to="loc_us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation_081bb523-769b-44ac-8416-a1e08308a872" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinanceLeasePrincipalPayments_604f1089-4883-4fa4-83cd-1f0cf9e6d6e5" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_FinanceLeasePrincipalPayments"/>
    <link:calculationArc order="3" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_6689d1a3-cc3e-4940-9908-0fa64be6257f" xlink:to="loc_us-gaap_FinanceLeasePrincipalPayments_604f1089-4883-4fa4-83cd-1f0cf9e6d6e5" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RepaymentsOfNotesPayable_f40248ab-2b60-494a-a26e-1f928c14c6cb" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RepaymentsOfNotesPayable"/>
    <link:calculationArc order="4" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_6689d1a3-cc3e-4940-9908-0fa64be6257f" xlink:to="loc_us-gaap_RepaymentsOfNotesPayable_f40248ab-2b60-494a-a26e-1f928c14c6cb" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromStockOptionsExercised_ca972f4a-f2f0-4b4b-9598-05bd01f41466" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ProceedsFromStockOptionsExercised"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_6689d1a3-cc3e-4940-9908-0fa64be6257f" xlink:to="loc_us-gaap_ProceedsFromStockOptionsExercised_ca972f4a-f2f0-4b4b-9598-05bd01f41466" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_2f700f44-24a1-4136-8bed-7945f6797bb3" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_cc0a5175-2290-4de2-9b71-51e500a42a33" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PaymentsToAcquirePropertyPlantAndEquipment"/>
    <link:calculationArc order="1" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_2f700f44-24a1-4136-8bed-7945f6797bb3" xlink:to="loc_us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_cc0a5175-2290-4de2-9b71-51e500a42a33" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.exagen.com/role/SummaryofSignificantAccountingPoliciesCashCashEquivalentsandRestrictedCashDetails" xlink:type="simple" xlink:href="exdx-20230331.xsd#SummaryofSignificantAccountingPoliciesCashCashEquivalentsandRestrictedCashDetails"/>
  <link:calculationLink xlink:role="http://www.exagen.com/role/SummaryofSignificantAccountingPoliciesCashCashEquivalentsandRestrictedCashDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_a8c43cca-00fc-4d39-8496-a26b818ca221" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCash_f4f4873b-8d51-4d97-af9a-03f2951fa39a" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RestrictedCash"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_a8c43cca-00fc-4d39-8496-a26b818ca221" xlink:to="loc_us-gaap_RestrictedCash_f4f4873b-8d51-4d97-af9a-03f2951fa39a" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_39453f68-0fe5-4dc6-83c2-1d9e51635ee2" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_a8c43cca-00fc-4d39-8496-a26b818ca221" xlink:to="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_39453f68-0fe5-4dc6-83c2-1d9e51635ee2" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.exagen.com/role/OtherFinancialInformationPrepaidExpensesDetails" xlink:type="simple" xlink:href="exdx-20230331.xsd#OtherFinancialInformationPrepaidExpensesDetails"/>
  <link:calculationLink xlink:role="http://www.exagen.com/role/OtherFinancialInformationPrepaidExpensesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PrepaidExpenseAndOtherAssetsCurrent_37e63436-a07d-4717-af08-04abc02e614d" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PrepaidExpenseAndOtherAssetsCurrent"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_PrepaidMaintenanceAndInsuranceContracts_4df8b697-eb90-412c-89af-e69c4a79693a" xlink:href="exdx-20230331.xsd#exdx_PrepaidMaintenanceAndInsuranceContracts"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_PrepaidExpenseAndOtherAssetsCurrent_37e63436-a07d-4717-af08-04abc02e614d" xlink:to="loc_exdx_PrepaidMaintenanceAndInsuranceContracts_4df8b697-eb90-412c-89af-e69c4a79693a" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PrepaidRoyalties_77184e40-4682-42d0-8531-d664700e93a0" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PrepaidRoyalties"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_PrepaidExpenseAndOtherAssetsCurrent_37e63436-a07d-4717-af08-04abc02e614d" xlink:to="loc_us-gaap_PrepaidRoyalties_77184e40-4682-42d0-8531-d664700e93a0" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherPrepaidExpenseCurrent_15d67096-fb0b-460b-9fd9-118978131164" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OtherPrepaidExpenseCurrent"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_PrepaidExpenseAndOtherAssetsCurrent_37e63436-a07d-4717-af08-04abc02e614d" xlink:to="loc_us-gaap_OtherPrepaidExpenseCurrent_15d67096-fb0b-460b-9fd9-118978131164" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherAssetsCurrent_3af4398d-8aca-428c-9f86-04a6a63009ed" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OtherAssetsCurrent"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_PrepaidExpenseAndOtherAssetsCurrent_37e63436-a07d-4717-af08-04abc02e614d" xlink:to="loc_us-gaap_OtherAssetsCurrent_3af4398d-8aca-428c-9f86-04a6a63009ed" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.exagen.com/role/OtherFinancialInformationPropertyandEquipmentDetails" xlink:type="simple" xlink:href="exdx-20230331.xsd#OtherFinancialInformationPropertyandEquipmentDetails"/>
  <link:calculationLink xlink:role="http://www.exagen.com/role/OtherFinancialInformationPropertyandEquipmentDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentAndFinanceLeaseRightOfUseAssetAfterAccumulatedDepreciationAndAmortization_d70c2eda-d6fa-46df-9d04-e84a999a0542" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PropertyPlantAndEquipmentAndFinanceLeaseRightOfUseAssetAfterAccumulatedDepreciationAndAmortization"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentAndFinanceLeaseRightOfUseAssetBeforeAccumulatedDepreciationAndAmortization_831f2b97-66cd-4e09-940e-d68b551753e9" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PropertyPlantAndEquipmentAndFinanceLeaseRightOfUseAssetBeforeAccumulatedDepreciationAndAmortization"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentAndFinanceLeaseRightOfUseAssetAfterAccumulatedDepreciationAndAmortization_d70c2eda-d6fa-46df-9d04-e84a999a0542" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentAndFinanceLeaseRightOfUseAssetBeforeAccumulatedDepreciationAndAmortization_831f2b97-66cd-4e09-940e-d68b551753e9" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentAndFinanceLeaseRightOfUseAssetAccumulatedDepreciationAndAmortization_fb1aa142-571a-4c5f-a0d4-07b9e32bf8a8" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PropertyPlantAndEquipmentAndFinanceLeaseRightOfUseAssetAccumulatedDepreciationAndAmortization"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentAndFinanceLeaseRightOfUseAssetAfterAccumulatedDepreciationAndAmortization_d70c2eda-d6fa-46df-9d04-e84a999a0542" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentAndFinanceLeaseRightOfUseAssetAccumulatedDepreciationAndAmortization_fb1aa142-571a-4c5f-a0d4-07b9e32bf8a8" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.exagen.com/role/OtherFinancialInformationAccruedandOtherCurrentLiabilitiesDetails" xlink:type="simple" xlink:href="exdx-20230331.xsd#OtherFinancialInformationAccruedandOtherCurrentLiabilitiesDetails"/>
  <link:calculationLink xlink:role="http://www.exagen.com/role/OtherFinancialInformationAccruedandOtherCurrentLiabilitiesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccruedLiabilitiesCurrent_890963e5-3320-445f-97b2-c08d7a54079d" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AccruedLiabilitiesCurrent"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccruedSalariesCurrent_09028ec7-8158-44cb-9723-4a20bd165af5" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AccruedSalariesCurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AccruedLiabilitiesCurrent_890963e5-3320-445f-97b2-c08d7a54079d" xlink:to="loc_us-gaap_AccruedSalariesCurrent_09028ec7-8158-44cb-9723-4a20bd165af5" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_AccruedLiabilitiesClinicalStudyCurrent_e12421ff-0b11-4138-a9b7-78071846dfbe" xlink:href="exdx-20230331.xsd#exdx_AccruedLiabilitiesClinicalStudyCurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AccruedLiabilitiesCurrent_890963e5-3320-445f-97b2-c08d7a54079d" xlink:to="loc_exdx_AccruedLiabilitiesClinicalStudyCurrent_e12421ff-0b11-4138-a9b7-78071846dfbe" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinanceLeaseLiabilityCurrent_43b37d10-798a-49fd-9ab1-665490f4d1b6" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_FinanceLeaseLiabilityCurrent"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AccruedLiabilitiesCurrent_890963e5-3320-445f-97b2-c08d7a54079d" xlink:to="loc_us-gaap_FinanceLeaseLiabilityCurrent_43b37d10-798a-49fd-9ab1-665490f4d1b6" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_AccruedPurchaseGoodsAndServicesCurrent_f65fc284-a3b3-4846-a2e3-03dd2a127ca4" xlink:href="exdx-20230331.xsd#exdx_AccruedPurchaseGoodsAndServicesCurrent"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AccruedLiabilitiesCurrent_890963e5-3320-445f-97b2-c08d7a54079d" xlink:to="loc_exdx_AccruedPurchaseGoodsAndServicesCurrent_f65fc284-a3b3-4846-a2e3-03dd2a127ca4" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestPayableCurrent_b8cc91ff-49ee-45a5-9dd6-5689e6fb483a" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InterestPayableCurrent"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AccruedLiabilitiesCurrent_890963e5-3320-445f-97b2-c08d7a54079d" xlink:to="loc_us-gaap_InterestPayableCurrent_b8cc91ff-49ee-45a5-9dd6-5689e6fb483a" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccruedRoyaltiesCurrent_70ad964b-810b-4810-b99c-319faee36ac3" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AccruedRoyaltiesCurrent"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AccruedLiabilitiesCurrent_890963e5-3320-445f-97b2-c08d7a54079d" xlink:to="loc_us-gaap_AccruedRoyaltiesCurrent_70ad964b-810b-4810-b99c-319faee36ac3" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherAccruedLiabilitiesCurrent_43aca17c-6857-4909-b5bf-b39da469ed34" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OtherAccruedLiabilitiesCurrent"/>
    <link:calculationArc order="7" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AccruedLiabilitiesCurrent_890963e5-3320-445f-97b2-c08d7a54079d" xlink:to="loc_us-gaap_OtherAccruedLiabilitiesCurrent_43aca17c-6857-4909-b5bf-b39da469ed34" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CustomerRefundLiabilityCurrent_b974f1d0-c205-487b-9d91-841d6bd39d0e" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CustomerRefundLiabilityCurrent"/>
    <link:calculationArc order="8" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AccruedLiabilitiesCurrent_890963e5-3320-445f-97b2-c08d7a54079d" xlink:to="loc_us-gaap_CustomerRefundLiabilityCurrent_b974f1d0-c205-487b-9d91-841d6bd39d0e" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.exagen.com/role/BorrowingsFutureMinimumPaymentsDetails" xlink:type="simple" xlink:href="exdx-20230331.xsd#BorrowingsFutureMinimumPaymentsDetails"/>
  <link:calculationLink xlink:role="http://www.exagen.com/role/BorrowingsFutureMinimumPaymentsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_exdx_LongTermDebtIncludingUndiscountedInterest_660c63c2-cbaa-4b7a-a3f9-b9d9e018e0af" xlink:href="exdx-20230331.xsd#exdx_LongTermDebtIncludingUndiscountedInterest"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree_2189466a-4b17-40ce-bab7-49c62ca836a9" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_exdx_LongTermDebtIncludingUndiscountedInterest_660c63c2-cbaa-4b7a-a3f9-b9d9e018e0af" xlink:to="loc_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree_2189466a-4b17-40ce-bab7-49c62ca836a9" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalRemainderOfFiscalYear_a21ce77e-9d20-4a3d-aeb3-7fab57114357" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalRemainderOfFiscalYear"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_exdx_LongTermDebtIncludingUndiscountedInterest_660c63c2-cbaa-4b7a-a3f9-b9d9e018e0af" xlink:to="loc_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalRemainderOfFiscalYear_a21ce77e-9d20-4a3d-aeb3-7fab57114357" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo_c76ee4d0-03b1-46ab-b03e-cd047c3c3e12" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_exdx_LongTermDebtIncludingUndiscountedInterest_660c63c2-cbaa-4b7a-a3f9-b9d9e018e0af" xlink:to="loc_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo_c76ee4d0-03b1-46ab-b03e-cd047c3c3e12" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths_528fcbbb-47e7-4ff2-9193-d046931a871e" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_exdx_LongTermDebtIncludingUndiscountedInterest_660c63c2-cbaa-4b7a-a3f9-b9d9e018e0af" xlink:to="loc_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths_528fcbbb-47e7-4ff2-9193-d046931a871e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebt_e6da6caf-f827-439b-b452-e7a1602ac585" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongTermDebt"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentUnamortizedDiscountPremiumAndDebtIssuanceCostsNet_bd74ec98-4261-4ae8-9a97-3fe713c03024" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtInstrumentUnamortizedDiscountPremiumAndDebtIssuanceCostsNet"/>
    <link:calculationArc order="1" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LongTermDebt_e6da6caf-f827-439b-b452-e7a1602ac585" xlink:to="loc_us-gaap_DebtInstrumentUnamortizedDiscountPremiumAndDebtIssuanceCostsNet_bd74ec98-4261-4ae8-9a97-3fe713c03024" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_LongTermDebtUndiscountedInterestAmount_8aa27b5c-e4f6-4767-85d0-040cd6a70fe9" xlink:href="exdx-20230331.xsd#exdx_LongTermDebtUndiscountedInterestAmount"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LongTermDebt_e6da6caf-f827-439b-b452-e7a1602ac585" xlink:to="loc_exdx_LongTermDebtUndiscountedInterestAmount_8aa27b5c-e4f6-4767-85d0-040cd6a70fe9" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_exdx_LongTermDebtIncludingUndiscountedInterest_26eb31ff-f744-4ea4-8a45-c1f82021cfef" xlink:href="exdx-20230331.xsd#exdx_LongTermDebtIncludingUndiscountedInterest"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LongTermDebt_e6da6caf-f827-439b-b452-e7a1602ac585" xlink:to="loc_exdx_LongTermDebtIncludingUndiscountedInterest_26eb31ff-f744-4ea4-8a45-c1f82021cfef" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.exagen.com/role/FairValueMeasurementsDetails" xlink:type="simple" xlink:href="exdx-20230331.xsd#FairValueMeasurementsDetails"/>
  <link:calculationLink xlink:role="http://www.exagen.com/role/FairValueMeasurementsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsFairValueDisclosure_84c4344d-bff6-49af-bcb6-7837ce6865ad" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AssetsFairValueDisclosure"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsFairValueDisclosure_3c253844-8c89-41a2-9c8c-0010ddf90137" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CashAndCashEquivalentsFairValueDisclosure"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsFairValueDisclosure_84c4344d-bff6-49af-bcb6-7837ce6865ad" xlink:to="loc_us-gaap_CashAndCashEquivalentsFairValueDisclosure_3c253844-8c89-41a2-9c8c-0010ddf90137" xlink:type="arc"/>
  </link:calculationLink>
</link:linkbase>
