Thierry Henry and Patrick Vieira have pulled out of the France squad to face England on Wednesday.
The Barcelona striker suffered an injury during his side's 4-1 win over Valladolid on Sunday.
Henry has now withdrawn from the squad to face Fabio Capello's England in Paris.
Vieira is struggling with a leg problem and he has decided not to risk the injury.
"I am frustrated," admitted Vieira.
"I hope to be able to play next weekend for Inter, as it (the injury) is getting much better, but not to be playing on Wednesday is extremely disappointing."
The news is a further blow for France coach Raymond Domenech who has already lost Lyon striker Karim Benzema to injury.
Benzema sustained an ankle injury during Lyon's 4-2 win over Paris Saint Germain on Sunday and Juventus striker David Trezeguet has been drafted in as his replacement.
Trezeguet has been out of the picture for France with his last appearance coming against Scotland last February.
Meanwhile, Lens striker Loic Remy has also been added to the France squad for the first time.
The 21-year-old replaces Mathieu Valbuena who was forced to withdraw after suffering an adductor injury on Saturday.