South Africa's Quinton Fortune twisted his ankle during training with Manchester United and could be out of action for three weeks, or the remainder of the season depending on the severity of the injury.
Fortune missed the FA Cup clash against Fulham on Saturday which United won 2-1.
"It's a bad blow," said Sir Alex Ferguson on the Red Devils' official website. "On Wednesday just before lunch, he turned awkwardly and hes done his cartilage.
"It looks like he's going to have it operated on tonight, we're just waiting on the scans coming back.
"It's difficult to say how long he will be out for. It depends on how much damage there is, but its certainly cartilage. Sometimes with those injuries you can get players back in three weeks, hopefully thats the case this time.
Manchester's defensive frailties have been exposed this season and the exclusion of Fortune adds to a long list of suspended and injured defenders.
He joins Rio Ferdinand, Mikael Silvestre and Gary Neville on the sidelines when Porto visit the English champions on Tuesday evening for a second-leg Champions League game.