Full-back Hugo Keenan has left the Ireland camp after suffering a hand injury in training in Portugal on Tuesday.
The Leinster man had recovered from hip surgery and was set to line out for the first time since last summer's British and Irish Lions tour in Ireland's opening Guinness Six Nations game on Thursday week.
Keenan, 29, has been Ireland's first choice full-back since breaking into the team in 2020, and has won 49 international caps; he scored the series-winning try in the second Lions Test against Australia last July.
It's another blow for Andy Farrell's injury-hit squad ahead of their first-round match in Paris.
Versatile back Mack Hansen, who scored a hat-trick from full-back against Australia in November was already ruled out with a foot injury, while Jamie Osborne hasn't played since the Japan match in the autumn due to a shoulder injury.
Ulster's Jacob Stockdale, Leinster's Ciarán Frawley and Munster's Jack Crowley may come into the running for the 15 jersey against Les Bleus.
"Hugo Keenan will return to Ireland after sustaining a fractured thumb in training on Tuesday afternoon in Portugal," said the union, who also confirmed that Bundee Aki has been replaced in the squad by Ulster's uncapped centre Jude Postlethwaite.
Farrell is also without Hansen, Robbie Henshaw, Calvin Nash, Jimmy O'Brien, Shayne Bolton, Jordan Larmour, Andrew Porter,Ryan Baird, Jack Boyle, Paddy McCarthy and Tom Ahern due to injury.
Connacht centre Aki (above, c) has been cited by the URC for alleged comments aimed the match officials in last weekend's defeat to Leinster, while the IRFU says that it is "investigating the matter further internally and no additional comment will be made at this time.
"The IRFU does not tolerate any form of disrespect shown towards match officials and does not condone actions that fall below the standards expected of players representing Irish rugby."
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