Cardiff Blues duo Gethin Jenkins and Gareth Williams and Scarlets hooker Matthew Rees have all been ruled out of Wales’ Six Nations clash with France next Friday.
The trio have all failed to recover from injury ahead of the Round 3 encounter at the Millennium Stadium.
Jenkins has aggravated the calf injury that saw him miss the opening round defeat to England, while Williams has damaged knee ligaments and Rees is still struggling with a groin injury.
No timescale has been set for the length of the recovery process for any of the three players but the Welsh Rugby Union has confirmed that none of them will be fit in time to face France.
"Matthew is progressing well and will continue his rehab in camp with Wales," said Wales physio Mark Davies.
"He will undergo exhaustive testing over the next few days which will give us a clearer idea of when he may be available, but we can confirm that the France game will come too soon for him.
"Gethin has been scanned since leaving the field against Scotland and, as we thought, he has aggravated the calf injury which kept him out against England. At this stage we are not putting a time limit on his recovery, but again we know he will not take the field against France.
"Gareth (Williams) sustained medial ligament damage to his knee during the win over Scotland last weekend. He will undertake a rest and rehab programme and his progress will be re-assessed next week, but the injury rules him out of contention for the Friday night Test."
Injury to Jenkins is likely to see Ospreys prop Paul James continue at loosehead, while the absence of Williams and Rees opens the door for Huw Bennett or the uncapped Ken Owens to wear the No2 shirt against the unbeaten French.