Jack Collison and Andy King have joined fellow midfielder Joe Ledley on Gary Speed's injury list ahead of Wales' Euro 2012 qualifier with Switzerland.
Collison and King are suffering knee and back problems respectively and both midfielders are doubts for Tuesday's final qualifier with Bulgaria in Sofia.
Ledley (thigh) and centre-backs James Collins (knee) and Danny Collins (groin) will miss Wales' double-header.
Defender Lewin Nyatanga and midfielder Jonathan Williams have won late calls.
Queens Park Rangers centre-back Danny Gabbidon (knee) and Cardiff City striker Rob Earnshaw (thigh) had already been ruled out.
But midfielder Dave Edwards, who is yet to play under manager Gary Speed, returns.
Edwards has missed the last seven Wales internationals due to a long-standing back problem, but has started his last two club games.
The Wolverhampton Wanderers midfielder bolsters Speed's engine room that is missing key members Collison, Ledley and King.
David Vaughan has also hardly trained this week as the Sunderland midfielder has been suffering tonsillitis.
So Swansea City midfielder Joe Allen could be rewarded for his impressive displays in the Premier League with a first Wales start at his club home on Friday.
Crystal Palace's uncapped teenager Williams joins the squad for the first time as he, Allen, Vaughan, Edwards and Andrew Crofts in the battle to play with captain Aaron Ramsey in the Wales midfield.
Aston Villa's James and Stoke City's Danny Collins, who were on the bench in Wales' narrow defeat to England, played the full 90 minutes for their clubs on Saturday but pulled out on Monday.
Wales are bottom of 2012 European Qualifying Group G and are seeking a first win in five attempts against Switzerland, following four successive defeats, when they welcome Ottmar Hitzfeld's side to Swansea's Liberty Stadium on 7 October.
The Swiss are still in the hunt to qualify for the finals in Poland and Ukraine, knowing that a win in Swansea and victory over Montenegro in the final match will secure second place in the group and a place in the play-offs.
Wales, whose 2-1 triumph over Montenegro a few weeks ago was their first win in the group, have long given up on qualification, but providing they are victorious in both games and other results go their way, third place is within reach.
Bulgaria, who have lost only twice to Wales in six previous meetings, sacked manager Lothar Matthaus in September after successive defeats to England and Switzerland.
Wales squad to face Switzerland and Bulgaria
Goalkeepers: Wayne Hennessey (Wolverhampton Wanderers), Boaz Myhill (West Bromwich Albion - on loan at Birmingham City)
Defenders: Darcy Blake (Cardiff City), Chris Gunter (Nottingham Forest), Adam Matthews (Celtic), Neil Taylor (Swansea City), Ashley Williams (Swansea City), Lewin Nyatanga (Bristol City)
Midfielders: Joe Allen (Swansea City), Gareth Bale (Tottenham Hotspur), Jack Collison (West Ham United), Andrew Crofts (Norwich City), David Edwards (Wolverhampton Wanderers), Andy King (Leicester City), Aaron Ramsey (Arsenal), David Vaughan (Sunderland), Jonathan Williams (Crystal Palace)
Forwards: Craig Bellamy (Liverpool), Hal Robson-Kanu, Simon Church (both Reading), Steve Morison (Norwich City), Sam Vokes (Wolverhampton Wanderers)
Stand-by list: Lewis Price (Crystal Palace), Neal Eardley (Blackpool), Ashley Richards (Swansea City), Rhoys Wiggins (Charlton Athletic), David Cotterill (Swansea City), Andy Dorman (Crystal Palace), Jermaine Easter (Crystal Palace), Ched Evans (Sheffield United)