Ferdinand, 32, has been struggling with a back complaint throughout the campaign, but a calf injury picked up in the warm-up prior to the loss at Wolves in early February has meant he has been unable to help United in their quest for the Treble.
"Rio has been out for a few weeks now,'' said Ferguson. "We are not looking at this as a short-term situation. He has not started training yet. We will be lucky to get him back for some part of the season.''
The loss of such an experienced player will come as a huge blow to United as they battle on in the Premier League, Champions League and FA Cup with a seriously depleted rearguard.
Versatile defender John O'Shea has been ruled out for five weeks with the hamstring injury he picked up against Marseille in midweek and full-back Rafael is out for at least two weeks with a similar injury.
"Vidic won't make it,'' confirmed Ferguson. "He is showing good recovery for this week and should be OK after the international break but not enough for Saturday.''
He added: "It has been a bad spell for us. Only a few weeks ago we had every defender fit and things were looking great. It has all just fallen apart in the last week or so.
"Hopefully Jonny Evans may be fit for Saturday, even if it is a bit of a risk. He has trained all week but he has been out for such a long time.''
Ferdinand has struggled with a series of injury problems in recent seasons and lost the United captaincy to Nemanja Vidic at the start of the season due to his ongoing fitness issues.
The England centre-back's absences have also had a costly effect at international level. After being handed the armband by manager Fabio Capello it now appears he may have to give it back to John Terry on a long-term basis.