Shaun Wright-Phillips is set to have a knee operation that will rule him out of England's matches next month against Kazakhstan and Andorra as well as Sunday's Barclays Premier League finale against Bolton.
City's talisman winger has not played since coming off during the first leg of the UEFA quarter-final Cup tie in Hamburg last month and constant painful setbacks have continued to hamper his recovery.
Manager Mark Hughes said: "Shaun trained earlier in the week but he got a reaction so he'll have to see a specialist. He's obviously not available at the weekend and he may well have to have a wash-out of his knee in the close season. He needs to have it as soon as possible. That will enable him to start pre-season."
While the news is a blow to City fans among a bumper Sunday crowd hoping to wish one of their heroes well for the summer, it is also a concern for England manager Fabio Capello and his World Cup qualifying campaign.
England face the tricky trip to Kazakhstan on June 6 with a more routine date against Andorra in midweek.
Hughes added: "It's a shame for Shaun, he's worked really hard but he keeps on getting a bit of swelling any time he does any physical work. There's obviously some irritation in the knee that needs to be addressed."
Newly-elected Player of the Year Stephen Ireland and Micah Richards, both victims of gastric flu in midweek, are on the way to recovery and expected to be in the line-up for the City of Manchester Stadium sign-off game.
The Blues boss said: "Stevie's OK and Micah feels a lot better than he did yesterday so they should be available. John Webb, our fitness guy, was the only other one to catch it. We isolated them quickly."