Northern Ireland's Jonny Evans limped off in Saturday's hard-fought 2-1 Premier League win over Blackburn Rovers at Old trafford with a recurrence of a recent ankle injury.
United racked up a 10th consecutive league victory but are now short of options for the trip to the San Siro.
"It's a bit sore," Evans told MUTV. "I kicked the ground when I tried to make a long clearance and now it's a bit tender.
"I don't know (if I'll be ready for Tuesday's game). The doctor said he'd have a look at it on Sunday. We'll have a better idea then."
Evans had been pencilled in to replace experienced Serb Nemanja Vidic, who is suspended following his sending off in FIFA's World Club Cup in December.
Wes Brown and Gary Neville have already been ruled out of the game against the Italian champions.
"We've got some injuries of course," Ferguson told Setanta Sports after the win against Rovers.
"I just hope I can get two centre backs but at this moment in time it's very doubtful. Jonny Evans would have played on Tuesday but he's very doubtful."
"I'm hoping I'll have John O'Shea fit as I won't have Vidic, Neville or Brown either," he added.
O'Shea injured his heel against Fulham last Wednesday but Ferguson is hoping he will recover to partner Rio Ferdinand in defence against Jose Mourinho's side.
