<?xml version="1.0"?>
<ownershipDocument>

    <schemaVersion>X0609</schemaVersion>

    <documentType>4</documentType>

    <periodOfReport>2026-06-25</periodOfReport>

    <issuer>
        <issuerCik>0001833214</issuerCik>
        <issuerName>SAB Biotherapeutics, Inc.</issuerName>
        <issuerTradingSymbol>SABS</issuerTradingSymbol>
        <issuerForeignTradingSymbol></issuerForeignTradingSymbol>
    </issuer>

    <reportingOwner>
        <reportingOwnerId>
            <rptOwnerCik>0001825323</rptOwnerCik>
            <rptOwnerName>Kropotova Alexandra</rptOwnerName>
        </reportingOwnerId>
        <reportingOwnerAddress>
            <rptOwnerNonUSAddressFlag>false</rptOwnerNonUSAddressFlag>
            <rptOwnerStreet1>777 W 41ST STREET, SUITE 401</rptOwnerStreet1>
            <rptOwnerStreet2></rptOwnerStreet2>
            <rptOwnerCity>MIAMI BEACH</rptOwnerCity>
            <rptOwnerState>FL</rptOwnerState>
            <rptOwnerZipCode>33140</rptOwnerZipCode>
            <rptOwnerStateDescription></rptOwnerStateDescription>
        </reportingOwnerAddress>
        <reportingOwnerRelationship>
            <isDirector>false</isDirector>
            <isOfficer>true</isOfficer>
            <isTenPercentOwner>false</isTenPercentOwner>
            <isOther>false</isOther>
            <officerTitle>CHIEF MEDICAL OFFICER</officerTitle>
        </reportingOwnerRelationship>
    </reportingOwner>

    <aff10b5One>false</aff10b5One>

    <nonDerivativeTable>
        <nonDerivativeTransaction>
            <securityTitle>
                <value>Common Stock</value>
            </securityTitle>
            <transactionDate>
                <value>2026-06-25</value>
            </transactionDate>
            <transactionCoding>
                <transactionFormType>4</transactionFormType>
                <transactionCode>F</transactionCode>
                <equitySwapInvolved>false</equitySwapInvolved>
            </transactionCoding>
            <transactionAmounts>
                <transactionShares>
                    <value>988</value>
                    <footnoteId id="F1"/>
                </transactionShares>
                <transactionPricePerShare>
                    <footnoteId id="F1"/>
                </transactionPricePerShare>
                <transactionAcquiredDisposedCode>
                    <value>D</value>
                </transactionAcquiredDisposedCode>
            </transactionAmounts>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>42308</value>
                    <footnoteId id="F2"/>
                    <footnoteId id="F3"/>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                </directOrIndirectOwnership>
            </ownershipNature>
        </nonDerivativeTransaction>
    </nonDerivativeTable>

    <footnotes>
        <footnote id="F1">Represents shares of the Issuer's common stock (&quot;Common Stock&quot;) withheld to statisfy tax withholding requirements on the vesting of the Issuer's restricked stock units (&quot;RSUs&quot;).</footnote>
        <footnote id="F2">Includes 37,158 shares of Common Stock and 5,150 shares of Common Stock which remain subject to vesting of RSUs granted under the Issuer's 2021 Equity Incentive Plan, as amended.</footnote>
        <footnote id="F3">Each RSU represents a contingent right to receive one share of Common Stock.</footnote>
    </footnotes>

    <ownerSignature>
        <signatureName>/s/ Alexandra Kropotova</signatureName>
        <signatureDate>2026-06-26</signatureDate>
    </ownerSignature>
</ownershipDocument>
