Steven Taylor and Danny Welbeck have been ruled out of this summer's European Under 21 Championship.
Stuart Pearce named both men in his initial 23-man squad earlier this week but will now have to decide on two replacements.
The England boss has to submit his final list to Uefa on Monday ahead of the tournament in Sweden and news of injuries to Taylor and Welbeck will come as a major blow
Newcastle defender Taylor has been playing through the pain barrier with an Achilles problem in recent weeks.
He completed 90 minutes against Aston Villa on the final day of the Premier League season but aggravated the injury and has been unable to recover.
"I have done everything I can to try to get fit but the final scans have shown that I will not be able to play," said Taylor, who had been chosen as Pearce's captain.
Manchester United striker Welbeck is unavailable because of a knee complaint.