England midfielder Gareth Barry has been ruled out for up to four weeks with ankle ligament damage.
The Manchester City man suffered the injury in his side's 1-0 defeat to Tottenham on Wednesday and limped off after 57 minutes.
It is a major setback to his plans to compete in this summer's World Cup, as the South Africa tournament is due to kick-off in five weeks time.
Barry has been a key player for England under Fabio Capello and his absence would be a major blow for the Three Lions.
The initial diagnosis of the knock was that the 29-year-old had only suffered a sprained ankle but tests on Friday revealed the injury was worse than first feared.
Capello has regularly insisted that he will only consider fully-fit players in his 23-man squad for the competition, which he will name on 1st June.
City manager Roberto Mancini said: "I feel very sorry for him.
"Gareth is a fantastic guy and a fantastic player.
"I hope he can play in the World Cup but Fabio Capello and his medical staff must decide.
"I don't know exactly how bad (the injury is), maybe three to four weeks, so I hope he can still go.
"He deserves to play in the World Cup."
If Barry does miss out then the Italian tactician could turn to the likes of Tom Huddlestone, Owen Hargreaves or even Scott Parker as cover in the holding role.
Do you think Gareth Barry will be fit for the World Cup?