John Terry and Frank Lampard will miss England's European Championship qualifiers against Bulgaria and Switzerland after both picked up injuries in Chelsea's 2-0 win against Stoke at Stamford Bridge.
Terry has a hamstring injury, while Lampard will undergo a hernia operation on Tuesday or Wednesday next week and is expected to be out for a fortnight.
"John Terry has tonight been ruled out of England's next two games due to injuries to his right hamstring and glute muscles," said a statement on the Chelsea website.
"John has spoken personally to the England management team, and Chelsea and England medical staff have also been in touch. All are agreed that John's injuries, that he has carried since pre-season, would benefit from a period of rest and rehabilitation."
Chelsea manager Carlo Ancelotti said on Frank Lampard: ''It is a very easy surgery but he has started to feel pain and he needs to have the operation. We have already spoken with the national team to explain the situation.''
Fulham striker Bobby Zamora is also unlikely to be available for England after going off in the second half against Blackpool with a thigh injury.
Manager Mark Hughes said: ''Bobby went really stiff at half time. He thought it was just a bang on the muscle and went out again. But he could not shake it off.
''I think he must be a doubt (for England) unfortunately. He was really looking forward to getting a chance. I will imagine he will go and be assessed by the England medical team and we will receive the information as quickly as we can. But at the moment he looks doubtful.''
Goalkeeper David Stockdale, who is believed to be a candidate for England, is also likely to ruled out.
Hughes explained: ''David has come in and done really well. But he has gone over on his ankle. He has got to be a doubt. It will be a real shame if he cannot stay with the group if he is picked.''
Tottenham boss Harry Redknapp says Peter Crouch is a doubt as he was withdrawn at half-time of the 1-0 loss at White Hart Lane.
''I think he might have done a rib; he was in agony at half-time. He's not sure if he's broken a rib or what he did but he was in pain.''