Portugal midfielder Maniche and playmaker Deco have been ruled out of the next two World Cup Group One qualifiers in Sweden and Albania.
The Football Federation said on its website (www.fpf.pt) on Tuesday that Maniche and Deco had not recovered from injuries sustained at their clubs Atletico Madrid and Chelsea.
They are the latest additions to an injury list that already included Chelsea central defender Ricardo Carvalho and Atletico midfielder Simao Sabrosa.
Portugal, who are fourth in the group with three points from two matches, play Sweden in Stockholm on Saturday before hosting Albania in Braga four days later.
Goalkeepers: Quim (Benfica), Eduardo Carvalho (Braga), Daniel Fernandes (VfL Bochum)
Defenders: Jose Bosingwa (Chelsea), Paulo Ferreira (Chelsea), Fernando Meira (Galatasaray), Bruno Alves (Porto), Pepe (Real Madrid), Vitorino Antunes (Lecce), Miguel (Valencia), Tonel (Sporting)
Midfielders: Raul Meireles (Porto), Joao Moutinho (Sporting), Carlos Martins (Benfica), Danny (Zenit St Petersburg), Yannick Djalo (Sporting), Manuel Fernandes (Valencia)
Forwards: Cristiano Ronaldo (Manchester United), Nuno Gomes (Benfica), Hugo Almeida (Werder Bremen), Nani (Manchester United), Ricardo Quaresma (Inter Milan).