Leigh Halfpenny has been ruled out of Wales' opening Six Nations game away to France in Paris on Friday, 1 February.
The 30-year-old British and Irish Lions back has not played since suffering concussion in the win over Australia on 10 November.
That could leave Wales short at full-back, as fellow Lion Liam Williams has missed training with a broken finger.
Scrum-half Gareth Davies and centre Scott Williams remain major injury doubts to face Les Bleus.
Scarlets lock Jake Ball, 27, is the only player in the 39-man squad released to play for his region this weekend.
His team-mate Rhys Patchell has been sidelined with a hamstring injury, but Scarlets say the 25-year-old back is "about a week or two away" from a return - giving him a chance of figuring at Stade de France.
Back-row Ross Moriarty and lock Adam Beard are still recovering from concussion and remain doubtful.
With Lions and Bath back-row Taulupe Faletau likely to miss the tournament with a broken arm, the availability of Moriarty has added importance.
Wales coach Warren Gatland suggested that Halfpenny, who has won 80 caps for his country and scored 713 points, is also likely to miss the second game against Italy in Rome on 9 February.
"We probably won't consider Leigh Halfpenny for the first couple of games," he said.
"He is making progress and improving. We are mindful at the moment that he is a bit symptomatic with headaches but he has been taking part in training.
"For us it's about easing him back in slowly. Hopefully he starts taking a more regular part in training and potentially look at including him towards the end of the tournament.
"He's been doing a lot of one-on-one work with Neil Jenkins with his kicking, so that's been a good distraction for him.
"There's no pressure from us in trying to rush him back. The most important thing is his health and safety and things are all right.
Wales have big injury concerns for scrum-half Gareth Davies and centre Scott Williams ahead of France
"Gareth Davies has a quad (thigh muscle) strain, Liam Williams has a broken finger and hasn't taken part in some training.
"A couple of concussions with Ross Moriarty, who should be back training; Adam Beard still has a few symptoms from concussion.
"Scott Williams is struggling (with an ankle injury) for the first game."
Despite the injury concerns, Gatland is confident of his side's chances as he takes charge of Wales for the last time in the Six Nations before he steps down after the 2019 World Cup.
Wales are unbeaten in nine Tests, their longest winning streak since 1999, after completing their first clean sweep of autumn fixtures that included wins over Australia, South Africa and Scotland.
"We're pleased where we are at the moment, we honestly believe that if we can win that first game against on Friday night we've got a great chance of winning the Six Nations," he said.
"The first two games we're away from home and then we've got England and Ireland at home, so we feel we've got a great opportunity.
"We finished second in the Six Nations last year and have had a great year. We just feel like we're in a good place."
Forwards: Rob Evans (Scarlets), Wyn Jones (Scarlets), Nicky Smith (Ospreys), Elliot Dee (Dragons), Ryan Elias (Scarlets), Ken Owens (Scarlets), Leon Brown (Dragons), Tomas Francis (Exeter Chiefs), Samson Lee (Scarlets), Dillon Lewis (Cardiff Blues), Jake Ball (Scarlets), Adam Beard (Ospreys), Seb Davies (Cardiff Blues), Cory Hill (Dragons), Alun Wyn Jones (captain, Ospreys) Ross Moriarty (Dragons), Josh Navidi (Cardiff Blues), Justin Tipuric (Ospreys), Josh Turnbull (Cardiff Blues), Aaron Wainwright (Dragons), Thomas Young (Wasps).
Backs: Aled Davies (Ospreys), Gareth Davies (Scarlets), Tomos Williams (Cardiff Blues), Gareth Anscombe (Cardiff Blues), Dan Biggar (Northampton), Jarrod Evans (Cardiff Blues), Rhys Patchell (Scarlets), Jonathan Davies (Scarlets), Hadleigh Parkes (Scarlets), Owen Watkin (Ospreys), Scott Williams (Ospreys), Josh Adams (Worcester), Hallam Amos (Dragons), Steffan Evans (Scarlets), Leigh Halfpenny (Scarlets), Jonah Holmes (Leicester), George North (Ospreys), Liam Williams (Saracens).