Head coach Andy Farrell was expected to name an unchanged starting XV for the visit to Paris before influential fly-half Sexton sustained the injury in training.
Munster’s Joey Carbery will deputise in the number 10 jersey, while Connacht’s Jack Carty will serve as back up at Stade de France.
Leinster lock James Ryan will skipper the side in Sexton’s absence.
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British and Irish Lions Iain Henderson and Robbie Henshaw return to the Irish bench following injuries in the only other changes from last weekend’s bonus-point win over Wales in Dublin.
Leinster second-row Ryan Baird and Ulster centre James Hume drop out of the matchday squad.
Carbery impressed as understudy in the autumn after Sexton was injured in the 29-20 win over New Zealand.
The 26-year-old – who suffered a fractured elbow in December – came off the bench to kick three crucial penalties against the All Blacks, before producing a man-of-the-match performance against Argentina a week later.
Ulster captain Henderson and Leinster centre Henshaw have each been restricted to limited game time this season.
Lock Henderson has not played since sustaining an ankle injury in his province’s Heineken Champions Cup win over Northampton on December 17 – his only outing since Ireland beat the Kiwis in November.
Henshaw has made just four appearances this season and missed some of his country’s pre-tournament training camp in Portugal due to a groin issue.
Despite the 2022 Six Nations being only one round old, this weekend’s clash in the French capital has already been billed as a potential title decider.
Pre-tournament favourites France lead the early standings ahead of Ireland after overcoming a slow start to defeat Italy 37-10 on Sunday.
Munster’s Tadhg Beirne seemed the man most at risk following Henderson’s return to fitness. He remains the only non-Leinster player in Farrell’s pack, partnering stand-in captain Ryan in the second row.
Hooker Ronan Kelleher continues alongside loosehead prop Andrew Porter and tighthead Tadhg Furlong, with Caelan Doris and Josh Van Der Flier either side of Jack Conan in the back row.
Scrum-half Jamison Gibson-Park will partner the incoming Carbery, with midfield duo Bundee Aki and Garry Ringrose keeping Henshaw on the bench.
Andrew Conway, who scored two tries against the Welsh, and Mack Hansen – the championship’s player of round one following his impressive Test debut – continue on the wings, with full-back Hugo Keenan starting his 18th consecutive international.
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