Craig Bellamy, Andrew Crofts and Neil Taylor have all been ruled out of Wales' opening 2014 World Cup qualifier against Belgium due to injury.
Cardiff City striker Bellamy has been forced to withdraw with a calf injury and his place in the squad has been taken by his club colleague Robert Earnshaw.
Brighton midfielder Crofts will also sit out Friday's game after picking up an ankle injury during his side's 3-1 win at Burnley on Saturday.
Left-back Taylor, meanwhile, will be sidelined for the bulk of Wales' qualifying campaign after being ruled out for the rest of the season after breaking his ankle during Swansea's 2-2 draw with Sunderland.
Earnshaw is the only player called up as a replacement so far by Wales coach Chris Coleman, who has already been hit hard by injury problems.
Celtic's Joe Ledley (groin), Sunderland's David Vaughan (groin), Wolves keeper Wayne Hennessey (knee) and West Ham's Jack Collison (knee) were all absent from Coleman's initial 23-man selection.
Uncapped Crystal Palace midfielder Jonathan Williams was included in the squad, as was Leicester's Andy King.
Key trio Gareth Bale, Joe Allen and Aaron Ramsey are all available for the daunting clash with a Belgium squad including the likes of Vincent Kompany, Marouane Fellaini and Eden Hazard.