Joe Ledley, Ethan Ampadu, Tom Lawrence and Neil Taylor have withdrawn from the Wales squad for the China Cup.
New Dragons boss Ryan Giggs, who was already without Arsenal midfielder Aaron Ramsey for his first games in charge, has called in Sunderland defender Adam Matthews.
The Football Association of Wales confirmed the news on its Twitter page, giving no reasons for the withdrawals.
Wales face hosts China on Thursday, March 22 and either Uruguay or Czech Republic on Monday, March 26.