Gareth Bale, the world's most expensive player, was named on Thursday in the Wales squad for the World Cup qualifiers against Macedonia and Belgium later this month despite a thigh injury.
But Wales manager Chris Coleman said the 24-year-old forward would not play in either match.
"We have spoken to the doctor and we will be without him, but we said all along it is very tough for him to have had no pre-season and be thrown in at the deep end," Coleman said.
Bale missed Spanish giants Real's 4-0 Champions League win over FC Copenhagen on Wednesday with the injury.
It was the second time in two weeks Bale has been sidelined by a thigh problem as he also missed the league matches against Getafe and Elche.
Bale joined Real Madrid from Tottenham Hotspur last month in a deal widely reported to be the world's most expensive transfer at around £86 million (100 million euros, $132.5 million).
Meanwhile Wales captain Ashley Williams is a fitness doubt due the ankle ligament injury which has kept him out of Swansea's recent matches.
Veteran Cardiff striker Craig Bellamy was included for what could be his final competitive games for Wales, with the striker having indicated he is unlikely to feature in the Euro 2016 qualifying campaign.
Last month's 2-1 defeat by Macedonia in Skopje ended Wales' slim hopes of qualifying for next year's World Cup finals in Brazil, with their last appearance in the latter stages of a major tournament way back at the 1958 World Cup in Sweden.
The result was made all the worse for Coleman after a lost passport meant he missed Wales' final pre-match preparations.
Wales squad for World Cup qualifying matches with Macedonia in Cardiff on October 11 and Belgium in Brussels on October 15:
Goalkeepers: Wayne Hennessey (Wolverhampton Wanderers/ENG), Glyn Myhill (West Bromwich Albion/ENG), Owain Fon Williams (Tranmere Rovers/ENG)
Defenders: Ben Davies (Swansea), Danny Gabbidon (Crystal Palace/ENG), Chris Gunter (Reading), Adam Matthews (Celtic/SCO), Samuel Ricketts (Wolverhampton Wanderers/ENG), Neil Taylor (Swansea), Ashley Williams (Swansea)
Midfielders: Joe Allen (Liverpool/ENG), Jack Collison (West Ham United/ENG, Loan AFC Bournemouth/ENG), Andrew Crofts (Brighton/ENG - Suspended v FYR Macedonia), Declan John (Cardiff City), Andy King (Leicester/ENG), Joe Ledley (Celtic/SCO), Aaron Ramsey (Arsenal/ENG), David Vaughan (Sunderland/ENG)
Forwards: Gareth Bale (Real Madrid/ESP), Craig Bellamy (Cardiff City), Simon Church (Charlton/ENG), Hal Robson-Kanu (Reading/ENG), Sam Vokes (Burnley/ENG)