Bath forwards Taulupe Faletau and Luke Charteris have been ruled out of Wales' Six Nations Championship opener against Italy.
Wales assistant coach Robin McBryde confirmed that No 8 Faletau, who is recovering from a knee injury, will not be fit in time for Sunday's Stadio Olimpico clash.
And McBryde also revealed that lock Charteris has a fracture in his hand.
It is thought, though, that both players will be in the selection frame for next week's clash with Six Nations title holders England.
Faletau was hurt during Bath's Aviva Premiership game against Wasps on Christmas Eve.
He missed three of Wales' four autumn Tests in November after suffering a knee injury on his Bath debut against Northampton two months previously.
Gloucester's Ross Moriarty will be favourite to wear the No 8 shirt against Italy.
Wales boss Rob Howley is due to name his starting line-up on Thursday, with Scarlets lock Jake Ball favourite to partner new team captain Alun Wyn Jones in the second row.
Asked about Faletau at the Wales training base on Tuesday, McBryde said: "He is still progressing. It is still early days. Everything is heading in the right direction there, really.
"(Fit) for this week? No, it will be too early this week."
And on Charteris, McBryde added: "He has a slight fracture in his hand, so he has been ruled out for this weekend as well. Hopefully, he will be fit for the following week."