Perpignan's David Marty has been called up by France to replace Toulouse centre Florian Fritz in Saturday's Six Nations opener against Scotland at Murrayfield.
Marty has won 19 caps for his country
Marty will be the sixth member of the France team which lost to England in the World Cup semi-final to face the Scots, while there are four new caps.
Fritz will miss the whole of France's Six Nations campaign after fracturing his lower leg in training.
The 24-year-old, capped 13 times, had been named in the starting XV.
"The forecast is a minimum of six weeks to three months out," team doctor Jean-Philippe Hager said.
The injury to Fritz comes the day after prop Jean-Baptiste Poux tore his thigh muscle and was sidelined for two weeks.
Fritz also missed last year's World Cup and his injury leaves France with only two other players in their 22-man squad, Damien Traille, who is already in the starting line-up, and replacement David Skrela, as cover at centre.
Fritz had a strong start to the season with Toulouse
Meanwhile, uncapped Francois Trinh-Duc will play at fly-half as one of four debutants in a much-changed side for France's opening Six Nations match against Scotland.
The 21-year-old is joined by Clermont wing Julien Malzieu, Sale prop Lionel Faure and Dax prop Julien Brugnaut.
Two more uncapped players, Albi lock Arnaud Mela and Bourgoin scrum-half Morgan Parra, are on the bench.
Fulgence Ouedraogo, capped once, is at flanker, while Loic Jacquet partners new captain Lionel Nallet at lock.
Ouedraogo is favoured ahead of Julien Bonnaire, a stand-out performer at the recent World Cup, who has to settle for a place on the bench.
Toulouse hooker William Servat has beaten Dimitri Szarzewski, of Stade Francais, to the starting role.
Cedric Heymans, a winger by trade, will fill in at full-back, while Damien Traille will be at centre in the absence of Yannick Jauzion.
With Poux (quadriceps) ruled out injured, Nicolas Mas has been called up and is on the bench.
France, with new coach Marc Lievremont at the helm, are aiming to defend the Six Nations title they have won the last two years.
Only six players from the World Cup squad remain in the starting XV, but Lievremont, who previously coached France's Under-21 side, is confident that Trinh-Duc among others have the quality to shine.
"Some could say that he lacks experience for this (fly-half) position, but he must start one day," the coach said.
"We have spoken a lot about confidence and taking responsibility - that is the case with him."
France: Heymans (Toulouse); Malzieu (Clermont Auvergne), Marty (Perpignan), Traille (Biarritz), Clerc (Toulouse); Trinh-Duc (Montpellier), J-B Elissalde (Toulouse); Faure (Sale), Servat (Toulouse), Brugnaut (Dax), Nallet (Castres, capt), Jacquet (Clermont Auvergne), Ouedraogo (Montpellier), Dusautoir (Toulouse), Vermeulen (Clermont Auvergne).
Replacements: Mas (Perpignan), Szarzewski (Stade Francais), Mela (Albi), Bonnaire (Clermont Auvergne), Parra (Bourgoin), Skrela (Stade Francais), Rougerie (Clermont Auvergne).