Centre Virimi Vakatawa is likely to miss two of France's opening Six Nations games with knee ligament damage, sources told AFP on Monday.
Vakatawa, 28, who has scored 10 tries in 27 Test appearances, suffered the injury in Racing 92's Top 14 loss to Bordeaux-Begles on Saturday and will be out for between three and six weeks.
He will be sidelined for the tournament opener at Italy on February 6 and the match at Ireland a week later but could return for the following games against Scotland, England and Wales.
Lyon's Pierre-Louis Barassi had already been named as the New Zealand-born midfielder's replacement.
Earlier, the French Rugby Federation announced three forwards have withdrawn from the squad including experienced prop Uini Atonio.
Atonio, 30, who weighs 145kg, has been replaced by Toulouse's Dorian Aldgheri while there are call-ups for uncapped Thierry Paiva and Thomas Pavault.
Bordeaux-Begles' tight-head Paiva comes in for Jean-Baptiste Gros and La Rochelle's Thomas Pavault takes the place of back-rower Swan Rebbadj, who pulled out of Toulon's Top 14 win on Sunday with a dental problem.
On Friday, Atonio and Lavault's clubmate Gregory Alldritt said he would undergo examinations on a knee injury this week instead of joining up with the Test side.
Full-back Thomas Ramos also withdrew from the squad last week with a groin injury and has been replaced by Vincent Rattez.
Fly-half Romain Ntamack is likely to miss the opening two games of the competition after undergoing surgery on a double jaw fracture he suffered on club duty late last month.