Wales are without forwards Gareth Williams, Gethin Jenkins and Matthew Rees for their RBS Six Nations match against France in Cardiff a week on Friday.
The WRU have confirmed that injuries will prevent all three from taking part - Williams, Jenkins and Rees suffering knee ligament, calf muscle and groin problems respectively.
Cardiff hooker Williams therefore becomes the third forward who started Wales' victory over Scotland on Saturday to be ruled out of their match against the tournament favourites.
Williams - who together with Jenkins limped out of the comeback win at the Millennium Stadium - follows flanker Andy Powell and lock Alun-Wyn Jones on to the sidelines.
The former was dropped earlier this week after being charged with drink-driving while Jones underwent an elbow operation on Wednesday.
Wales have also confirmed the continued absence of Scarlets hooker Rees, who has played no part in the tournament so far.
Head coach Warren Gatland is set to name his team to face the French on Monday, with Jonathan Thomas expected to move from lock to back-row as Powell's replacement.
However, Gatland must now also change the hooker - Huw Bennett would be favourite - and both second-row forwards, with Bradley Davies, Ian Gough and Luke Charteris favourites for inclusion.
Wales team physiotherapist Mark Davies said: "Matthew Rees is progressing well and will continue his rehab in camp with Wales.
"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 Jenkins 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 reassessed next week, but the injury rules him out of contention for the Friday night Test (against France)."
Meanwhile, Richie Rees is likely to start at scrum-half against France in place of his Cardiff Blues colleague Gareth Cooper.
But there is potentially some good news for Gatland with regard to the position, with Lions Mike Phillips and Dwayne Peel both on the comeback trail following injuries.
Phillips is due to be involved in the Ospreys' Magners League game against Connacht on Sunday, while Peel has been named as a starter for Sale Sharks when they meet Guinness Premiership opponents Leeds Carnegie on Friday.