France coach Bernard Laporte may be without his top two fly-halves for their RBS 6 Nations Championship title defence.
Julien Peyrelongue will definitely miss the tournament having been ruled out for at least two months with ligament damage to his right knee.
Frederic Michalak seriously injured his right ankle during Stade Toulousain's European 25-12 win over Northampton at the weekend. He is likely to miss at least a month although it could be longer which would rule him out of the start of the tournament.
"Fred avoided the worst, that is to say an operation, but his ankle, which was already very fragile, suffered a nasty twist and he will need a lot of time to recover," club doctor Albert Sadacca told French sports daily L'Equipe.
"He will be out for four weeks at best, but it could be up to six or eight weeks at worst."
Peyrelongue said he was bitterly disappointed at not being able to play for France in February and March.
"This is a big frustration for me," he added.
"But I think about my club first and, who knows, I might be able to play in the last two Six Nations matches."
Laporte is not as optimistic.
"We are now deprived of two No 10s with the tournament approaching very fast," said Laporte, whose prime objective is to forget about last month's Test matches which saw Les Bleus lose two out of three.
"For Julien it is clear the game is over. For Michalak his four-week minimum absence is huge.
"I think it will be tough to think he will play against Scotland (on February 5 at the Stade de France).
"I watched Stade Toulousain's match on television and when I saw the images of his injury it hurt.
"That type of injury is very problematic because the player is unable to run. Even if he works hard he will lose physical fitness."
Laporte is already thinking about a replacement.
"Fly-half is one of the positions we have been investigating for a while," he added.
"We said after the (autumn) Tests that things had to change and we are going to look around.
"However, we know we won't have 50 guys able to replace them. But there is (Yann) Delaigue, (David) Skrela and (Benjamin) Boyet."
Wales' acting head coach Rob Howley has given Sam Davies and Rory Thornton a boost ahead of the RBS 6 Nations by naming the uncapped Ospreys duo in his largely experienced squad for the Autumn Internationals.