Liverpool captain Steven Gerrard could be out for three to four weeks with the hamstring problem sustained on England duty, according to the club's medical team.
The 30-year-old will undergo a scan but Dr Peter Brukner, head of sports medicine and sports science, confirmed the midfielder's injury was "significant".
"Steven injured his hamstring last (Wednesday) night. He's just been in for an early assessment here and it certainly looks like a significant hamstring injury," said Brukner. "We should have the results of the scan tonight. He's going to be out for a little while, I'm afraid. I'd imagine it could be three to four weeks."
Gerrard was expected to play for an hour in Wednesday night's 2-1 defeat to France in a friendly at Wembley but was kept on longer because of injuries to other players. However, with five minutes to go he too was forced off after damaging his hamstring.
It provoked an angry response from Liverpool's head of fitness and conditioning Darren Burgess, who made his feelings clear on social networking site Twitter before quickly deleting his comments.
"Unbelievable from all associated with England and English FA with regard to Steven Gerrard's injury. Completely ignored agreement and past history," he said. "Completely amateurish and now we pay for their incompetence. Absolutely disgraceful."
However, Brukner took a more reasoned approach, accepting that the club could not dictate to England coach Fabio Capello how long Gerrard should have stayed on.
"If you put your hand up to play for your country, you've got to accept how long they want you to play for," he added.
"There were obviously circumstances last night which came together to result in Steven playing for a bit longer than we'd hoped, which is disappointing but there's nothing we can do about that now.
"We'll move on and work as hard as we can to get him back playing for Liverpool as soon as possible."