Taulupe Faletau and Luke Charteris have been ruled out of Wales' Six Nations opener at Italy this weekend.
Powerhouse number eight Faletau has not played since injuring his knee in Bath's defeat to Wasps in the Champions Cup at the end of September.
It was hoped that he would recover in time for the trip to Rome, but forwards coach Robin McBryde told a news conference on Tuesday that the match will come too soon.
"It's too early for him this week. There's good competition there. We're in a healthy place at the moment," McBryde said.
"Whoever gets the nod, I'm sure he'll perform on the day. He will be in contention to face England [on February 11].
"It's a big blow for Taulupe. If he's not playing there's an opportunity for someone else.
"Nobody likes to be injured for a game, especially a Six Nations opener."
Lock Charteris, Faletau's Bath club-mate, is also unavailable after sustaining a fracture in his hand, but McBryde hopes he will also be fit to face defending champions England at the Principality Stadium.
"Luke Charteris has picked up a slight fracture in his hand so he's been ruled out of this weekend, but hopefully he'll be fit for the following week," McBryde added.