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

    <schemaVersion>X0206</schemaVersion>

    <documentType>3</documentType>

    <periodOfReport>2021-05-27</periodOfReport>

    <noSecuritiesOwned>0</noSecuritiesOwned>

    <issuer>
        <issuerCik>0001847903</issuerCik>
        <issuerName>Centessa Pharmaceuticals plc</issuerName>
        <issuerTradingSymbol>CNTA</issuerTradingSymbol>
    </issuer>

    <reportingOwner>
        <reportingOwnerId>
            <rptOwnerCik>0001601521</rptOwnerCik>
            <rptOwnerName>De Rubertis Francesco</rptOwnerName>
        </reportingOwnerId>
        <reportingOwnerAddress>
            <rptOwnerStreet1>C/O CENTESSA PHARMACEUTICALS PLC</rptOwnerStreet1>
            <rptOwnerStreet2>3RD FL., 1 ASHLEY RD, ALTRINCHAM</rptOwnerStreet2>
            <rptOwnerCity>CHESHIRE</rptOwnerCity>
            <rptOwnerState>X0</rptOwnerState>
            <rptOwnerZipCode>WA14 2DT</rptOwnerZipCode>
            <rptOwnerStateDescription>UNITED KINGDOM</rptOwnerStateDescription>
        </reportingOwnerAddress>
        <reportingOwnerRelationship>
            <isDirector>1</isDirector>
            <isOfficer>0</isOfficer>
            <isTenPercentOwner>0</isTenPercentOwner>
            <isOther>0</isOther>
        </reportingOwnerRelationship>
    </reportingOwner>

    <nonDerivativeTable>
        <nonDerivativeHolding>
            <securityTitle>
                <value>Ordinary Shares</value>
                <footnoteId id="F1"/>
                <footnoteId id="F2"/>
            </securityTitle>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>4398519</value>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>I</value>
                </directOrIndirectOwnership>
                <natureOfOwnership>
                    <value>See footnote</value>
                    <footnoteId id="F3"/>
                </natureOfOwnership>
            </ownershipNature>
        </nonDerivativeHolding>
        <nonDerivativeHolding>
            <securityTitle>
                <value>Ordinary Shares</value>
                <footnoteId id="F1"/>
                <footnoteId id="F2"/>
            </securityTitle>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>55677</value>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>I</value>
                </directOrIndirectOwnership>
                <natureOfOwnership>
                    <value>See footnote</value>
                    <footnoteId id="F4"/>
                </natureOfOwnership>
            </ownershipNature>
        </nonDerivativeHolding>
        <nonDerivativeHolding>
            <securityTitle>
                <value>Ordinary Shares</value>
                <footnoteId id="F1"/>
                <footnoteId id="F2"/>
            </securityTitle>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>1268542</value>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>I</value>
                </directOrIndirectOwnership>
                <natureOfOwnership>
                    <value>See footnote</value>
                    <footnoteId id="F5"/>
                </natureOfOwnership>
            </ownershipNature>
        </nonDerivativeHolding>
        <nonDerivativeHolding>
            <securityTitle>
                <value>Ordinary Shares</value>
                <footnoteId id="F1"/>
                <footnoteId id="F2"/>
            </securityTitle>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>30136</value>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>I</value>
                </directOrIndirectOwnership>
                <natureOfOwnership>
                    <value>See footnote</value>
                    <footnoteId id="F6"/>
                </natureOfOwnership>
            </ownershipNature>
        </nonDerivativeHolding>
        <nonDerivativeHolding>
            <securityTitle>
                <value>Ordinary Shares</value>
                <footnoteId id="F1"/>
                <footnoteId id="F2"/>
            </securityTitle>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>9403092</value>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>I</value>
                </directOrIndirectOwnership>
                <natureOfOwnership>
                    <value>See footnote</value>
                    <footnoteId id="F7"/>
                </natureOfOwnership>
            </ownershipNature>
        </nonDerivativeHolding>
        <nonDerivativeHolding>
            <securityTitle>
                <value>Ordinary Shares</value>
                <footnoteId id="F1"/>
                <footnoteId id="F2"/>
            </securityTitle>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>236108</value>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>I</value>
                </directOrIndirectOwnership>
                <natureOfOwnership>
                    <value>See footnote</value>
                    <footnoteId id="F8"/>
                </natureOfOwnership>
            </ownershipNature>
        </nonDerivativeHolding>
    </nonDerivativeTable>

    <derivativeTable>
        <derivativeHolding>
            <securityTitle>
                <value>Series A Preferred Shares</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <footnoteId id="F9"/>
            </conversionOrExercisePrice>
            <exerciseDate>
                <footnoteId id="F9"/>
            </exerciseDate>
            <expirationDate>
                <footnoteId id="F9"/>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Ordinary Shares</value>
                    <footnoteId id="F2"/>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>1886990</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>I</value>
                </directOrIndirectOwnership>
                <natureOfOwnership>
                    <value>See footnote</value>
                    <footnoteId id="F5"/>
                </natureOfOwnership>
            </ownershipNature>
        </derivativeHolding>
        <derivativeHolding>
            <securityTitle>
                <value>Series A Preferred Shares</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <footnoteId id="F9"/>
            </conversionOrExercisePrice>
            <exerciseDate>
                <footnoteId id="F9"/>
            </exerciseDate>
            <expirationDate>
                <footnoteId id="F9"/>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Ordinary Shares</value>
                    <footnoteId id="F2"/>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>44828</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>I</value>
                </directOrIndirectOwnership>
                <natureOfOwnership>
                    <value>See footnote</value>
                    <footnoteId id="F6"/>
                </natureOfOwnership>
            </ownershipNature>
        </derivativeHolding>
    </derivativeTable>

    <footnotes>
        <footnote id="F1">Represents A Ordinary Shares that will be redesignated as Ordinary Shares immediately prior to the closing of the initial public offering (&quot;IPO&quot;).</footnote>
        <footnote id="F2">Ordinary Shares may be represented by American Depositary Shares, each of which currently represents one Ordinary Share.</footnote>
        <footnote id="F3">Held by Medicxi Ventures I LP, a Jersey limited partnership (&quot;Medicxi Ventures I&quot;). Medicxi Ventures I GP Limited, a Jersey limited liability company (&quot;MVI GP&quot;), is the sole managing general partner of Medicxi Ventures I, and Medicxi Ventures Management (Jersey) Limited, a Jersey limited liability company (&quot;Medicxi Manager&quot;), is the sole manager of Medicxi Ventures I. The Reporting Person is a member of the board of directors of Medicxi Manager. The Reporting Person disclaims Section 16 beneficial ownership of the securities held by Medicxi Ventures I, except to the extent of his pecuniary interest therein, if any, and this report shall not be deemed to be an admission that he has beneficial ownership of such shares for Section 16 or any other purpose.</footnote>
        <footnote id="F4">Held by Medicxi Co-Invest I LP, a Jersey limited partnership (&quot;Medicxi Co-Invest I&quot;).  MVI GP is the sole managing general partner of Medicxi Co-Invest I, and Medicxi Manager is the sole manager of Medicxi Co-Invest I. The Reporting Person is a member of the board of directors of Medicxi Manager. The Reporting Person disclaims Section 16 beneficial ownership of the securities held by Medicxi Co-Invest I, except to the extent of his pecuniary interest therein, if any, and this report shall not be deemed to be an admission that he has beneficial ownership of such shares for Section 16 or any other purpose.</footnote>
        <footnote id="F5">Held by Medicxi Growth I LP, a Jersey limited partnership (&quot;Medicxi Growth I&quot;). Medicxi Growth I GP Limited, a Jersey limited liability company (&quot;MGI GP&quot;), is the sole managing general partner of Medicxi Growth I, and Medicxi Manager is the sole manager of Medicxi Growth I. The Reporting Person is a member of the board of directors of Medicxi Manager. The Reporting Person disclaims Section 16 beneficial ownership of the securities held by Medicxi Growth I, except to the extent of his pecuniary interest therein, if any, and this report shall not be deemed to be an admission that he has beneficial ownership of such shares for Section 16 or any other purpose.</footnote>
        <footnote id="F6">Held by Medicxi Growth Co-Invest I LP, a Jersey limited partnership (&quot;Medicxi Growth Co-Invest I&quot;). MGI GP is the sole managing general partner of Medicxi Growth Co-Invest I, and Medicxi Manager is the sole manager of Medicxi Growth Co-Invest I. The Reporting Person is a member of the board of directors of Medicxi Manager. The Reporting Person disclaims Section 16 beneficial ownership of the securities held by Medicxi Growth Co-Invest I, except to the extent of his pecuniary interest therein, if any, and this report shall not be deemed to be an admission that he has beneficial ownership of such shares for Section 16 or any other purpose.</footnote>
        <footnote id="F7">Held by Medicxi Secondary I LP, a Jersey limited partnership (&quot;Medicxi Secondary I&quot;). Medicxi Secondary I GP Limited, a Jersey limited liability company (&quot;MSI GP&quot;), is the sole managing general partner of Medicxi Secondary I, and Medicxi Manager is the sole manager of Medicxi Secondary I. The Reporting Person is a member of the board of directors of Medicxi Manager. The Reporting Person disclaims Section 16 beneficial ownership of the securities held by Medicxi Secondary I, except to the extent of his pecuniary interest therein, if any, and this report shall not be deemed to be an admission that he has beneficial ownership of such shares for Section 16 or any other purpose.</footnote>
        <footnote id="F8">Held by Medicxi Secondary Co-Invest I LP, a Jersey limited partnership (&quot;Medicxi Secondary Co-Invest I&quot;). MSI GP is the sole managing general partner of Medicxi Secondary Co-Invest I, and Medicxi Manager is the sole manager of and Medicxi Secondary Co-Invest I. The Reporting Person is a member of the board of directors of Medicxi Manager. The Reporting Person disclaims Section 16 beneficial ownership of the securities held by Medicxi Secondary Co-Invest I, except to the extent of his pecuniary interest therein, if any, and this report shall not be deemed to be an admission that he has beneficial ownership of such shares for Section 16 or any other purpose.</footnote>
        <footnote id="F9">Immediately prior to the closing of the IPO, Series A Preferred Shares will automatically convert on a one-to-one basis into Ordinary Shares without payment or further consideration. The resulting number of Ordinary Shares of the Issuer are shown in Column 3. The Series A Preferred Shares have no expiration date.</footnote>
    </footnotes>

    <remarks>Exhibit 24 - Power of Attorney</remarks>

    <ownerSignature>
        <signatureName>/s/ Marella Thorell, attorney-in-fact</signatureName>
        <signatureDate>2021-05-27</signatureDate>
    </ownerSignature>
</ownershipDocument>
