The Swansea defender has picked up an ankle ligament problem and will miss Friday's clash at Cardiff City Stadium as well as Tuesday's trip to face Group A leaders Belgium in Brussels.
Wales manager Chris Coleman is dealing with a long list of injuries and has already been forced to call up nine replacements for the two games.
Adam Matthews, Ben Davies, Gareth Bale, Danny Gabbidon, Sam Ricketts, Jack Collison, Joe Allen and Joe Ledley are all unavailable - meaning the likes of Owain Tudur Jones, Daniel Alfei, James Wilson, Rhoys Wiggins, Jermaine Easter, Lloyd Isgrove, David Cotterill, Jazz Richards and Shaun MacDonald are all included.
Wales sit rock-bottom of the Group heading into the clashes, but Football Association of Wales chief executive Jonathan Ford recently reiterated his faith in Coleman, who took over in January 2012.
Ford said: "We need to make sure we've got the right man in place. Personally I think Chris is doing a fantastic job, let's hope he stays with it."