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

    <schemaVersion>X0306</schemaVersion>

    <documentType>4</documentType>

    <periodOfReport>2021-09-08</periodOfReport>

    <issuer>
        <issuerCik>0001786248</issuerCik>
        <issuerName>NexPoint Real Estate Finance, Inc.</issuerName>
        <issuerTradingSymbol>NREF</issuerTradingSymbol>
    </issuer>

    <reportingOwner>
        <reportingOwnerId>
            <rptOwnerCik>0001228922</rptOwnerCik>
            <rptOwnerName>DONDERO JAMES D</rptOwnerName>
        </reportingOwnerId>
        <reportingOwnerAddress>
            <rptOwnerStreet1>300 CRESCENT COURT, SUITE 700</rptOwnerStreet1>
            <rptOwnerStreet2></rptOwnerStreet2>
            <rptOwnerCity>DALLAS</rptOwnerCity>
            <rptOwnerState>TX</rptOwnerState>
            <rptOwnerZipCode>75201</rptOwnerZipCode>
            <rptOwnerStateDescription></rptOwnerStateDescription>
        </reportingOwnerAddress>
        <reportingOwnerRelationship>
            <isDirector>1</isDirector>
            <isOfficer>1</isOfficer>
            <isTenPercentOwner>1</isTenPercentOwner>
            <officerTitle>President</officerTitle>
        </reportingOwnerRelationship>
    </reportingOwner>

    <derivativeTable>
        <derivativeTransaction>
            <securityTitle>
                <value>OP Units</value>
                <footnoteId id="F1"/>
            </securityTitle>
            <conversionOrExercisePrice>
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            <transactionDate>
                <value>2021-09-08</value>
            </transactionDate>
            <transactionCoding>
                <transactionFormType>5</transactionFormType>
                <transactionCode>J</transactionCode>
                <equitySwapInvolved>0</equitySwapInvolved>
                <footnoteId id="F3"/>
            </transactionCoding>
            <transactionAmounts>
                <transactionShares>
                    <value>3247509.69</value>
                </transactionShares>
                <transactionPricePerShare>
                    <value>0</value>
                    <footnoteId id="F3"/>
                </transactionPricePerShare>
                <transactionAcquiredDisposedCode>
                    <value>D</value>
                </transactionAcquiredDisposedCode>
            </transactionAmounts>
            <exerciseDate>
                <footnoteId id="F2"/>
            </exerciseDate>
            <expirationDate>
                <footnoteId id="F2"/>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>3247509.69</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>0</value>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>I</value>
                </directOrIndirectOwnership>
                <natureOfOwnership>
                    <value>See Footnote</value>
                    <footnoteId id="F4"/>
                </natureOfOwnership>
            </ownershipNature>
        </derivativeTransaction>
        <derivativeTransaction>
            <securityTitle>
                <value>OP Units</value>
                <footnoteId id="F1"/>
            </securityTitle>
            <conversionOrExercisePrice>
                <footnoteId id="F2"/>
            </conversionOrExercisePrice>
            <transactionDate>
                <value>2021-09-08</value>
            </transactionDate>
            <transactionCoding>
                <transactionFormType>5</transactionFormType>
                <transactionCode>J</transactionCode>
                <equitySwapInvolved>0</equitySwapInvolved>
                <footnoteId id="F3"/>
            </transactionCoding>
            <transactionAmounts>
                <transactionShares>
                    <value>395033.86</value>
                </transactionShares>
                <transactionPricePerShare>
                    <value>0</value>
                    <footnoteId id="F3"/>
                </transactionPricePerShare>
                <transactionAcquiredDisposedCode>
                    <value>D</value>
                </transactionAcquiredDisposedCode>
            </transactionAmounts>
            <exerciseDate>
                <footnoteId id="F2"/>
            </exerciseDate>
            <expirationDate>
                <footnoteId id="F2"/>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>395033.86</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>0</value>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>I</value>
                </directOrIndirectOwnership>
                <natureOfOwnership>
                    <value>See Footnote</value>
                    <footnoteId id="F5"/>
                </natureOfOwnership>
            </ownershipNature>
        </derivativeTransaction>
        <derivativeTransaction>
            <securityTitle>
                <value>Class B OP Units</value>
                <footnoteId id="F1"/>
            </securityTitle>
            <conversionOrExercisePrice>
                <footnoteId id="F2"/>
            </conversionOrExercisePrice>
            <transactionDate>
                <value>2021-09-08</value>
            </transactionDate>
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                <transactionFormType>5</transactionFormType>
                <transactionCode>J</transactionCode>
                <equitySwapInvolved>0</equitySwapInvolved>
                <footnoteId id="F3"/>
            </transactionCoding>
            <transactionAmounts>
                <transactionShares>
                    <value>3247509.69</value>
                </transactionShares>
                <transactionPricePerShare>
                    <value>0</value>
                    <footnoteId id="F3"/>
                </transactionPricePerShare>
                <transactionAcquiredDisposedCode>
                    <value>A</value>
                </transactionAcquiredDisposedCode>
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            <exerciseDate>
                <footnoteId id="F2"/>
            </exerciseDate>
            <expirationDate>
                <footnoteId id="F2"/>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>3247509.69</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>3247509.69</value>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>I</value>
                </directOrIndirectOwnership>
                <natureOfOwnership>
                    <value>See Footnote</value>
                    <footnoteId id="F4"/>
                </natureOfOwnership>
            </ownershipNature>
        </derivativeTransaction>
        <derivativeTransaction>
            <securityTitle>
                <value>Class C OP Units</value>
                <footnoteId id="F1"/>
            </securityTitle>
            <conversionOrExercisePrice>
                <footnoteId id="F2"/>
            </conversionOrExercisePrice>
            <transactionDate>
                <value>2021-09-08</value>
            </transactionDate>
            <transactionCoding>
                <transactionFormType>5</transactionFormType>
                <transactionCode>J</transactionCode>
                <equitySwapInvolved>0</equitySwapInvolved>
                <footnoteId id="F3"/>
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            <transactionAmounts>
                <transactionShares>
                    <value>395033.86</value>
                </transactionShares>
                <transactionPricePerShare>
                    <value>0</value>
                    <footnoteId id="F3"/>
                </transactionPricePerShare>
                <transactionAcquiredDisposedCode>
                    <value>A</value>
                </transactionAcquiredDisposedCode>
            </transactionAmounts>
            <exerciseDate>
                <footnoteId id="F2"/>
            </exerciseDate>
            <expirationDate>
                <footnoteId id="F2"/>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>395033.86</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>395033.86</value>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>I</value>
                </directOrIndirectOwnership>
                <natureOfOwnership>
                    <value>See Footnote</value>
                    <footnoteId id="F5"/>
                </natureOfOwnership>
            </ownershipNature>
        </derivativeTransaction>
    </derivativeTable>

    <footnotes>
        <footnote id="F1">Represents common units of limited partnership interest (&quot;OP Units&quot;) in NexPoint Real Estate Finance Operating Partnership, L.P., the operating partnership (the &quot;OP&quot;) of NexPoint Real Estate Finance, Inc. (the &quot;Issuer&quot;).</footnote>
        <footnote id="F2">The OP Units are redeemable, subject to certain requirements, for cash or, at the election of the Issuer, for shares of the Issuer's common stock on a one-for-one basis. The OP Units were vested as of the date of issuance and have no expiration date.</footnote>
        <footnote id="F3">Pursuant to a reclassification exempt under Rule 16b-7 promulgated under the Securities Exchange Act of 1934, each OP Unit reported herein was reclassified into a new Class B OP Unit or Class C OP Unit.</footnote>
        <footnote id="F4">These OP Units are held by NexPoint Advisors, L.P. (&quot;NP&quot;) indirectly through advised accounts. Mr. Dondero is the sole member of NP's general partner, and may be deemed to be an indirect beneficial owner of securities held by NP. Mr. Dondero disclaims beneficial ownership of such securities except to the extent of his pecuniary interest therein.</footnote>
        <footnote id="F5">These securities are held by a trust, of which Mr. Dondero is the beneficiary. Mr. Dondero disclaims beneficial ownership of such securities.</footnote>
    </footnotes>

    <ownerSignature>
        <signatureName>/s/ Brian Mitts, as attorney-in-fact for James Dondero</signatureName>
        <signatureDate>2021-11-12</signatureDate>
    </ownerSignature>
</ownershipDocument>
