The 28-year-old has not played since returning to Old Trafford from international duty with the Republic of Ireland in November.
The versatile stopper believed he had sustained a dead leg and would be back in action for the Red Devils in a matter of days.
However, complications have since arisen, with United supremo Ferguson revealing that O'Shea has a blood clot in his leg and - in all likelihood - will not feature for the rest of 2009/10.
"He's got a terrible injury at the moment," Ferguson said in the Irish Independent.
"It's one of those sorts of injuries that are unusual. It's like a dead leg except a dead leg is usually only three or four days.
"The problem is that the blood clot became all knotted and when it gets knotted you get calcification so therefore it's a long process to clear that up and he'll probably miss the season now.
"It's a bad blow for the boy and for the team because he can play anywhere.
"When you look at all the problems I've had with the back four this season, he could have played every single one."
United's back-line has been decimated by injury this season, with Rio Ferdinand, Nemanja Vidic, Wes Brown, Jonny Evans, Fabio and Rafael da Silva and Gary Neville all joining O'Shea on the sidelines at various stages of the campaign.
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