With Nemanja Vidic suspended after being sent off for a second yellow card in Tuesday's 2-1 loss to Chelsea at Stamford Bridge, Wes Brown will play alongside the inexperienced Chris Smalling in central defence.
"[Rio] won't be fit. Wes will take over," Ferguson told the club's televsion channel MUTV. "He has great experience."
The 32-year-old Ferdinand injured his calf in the warm-up before United's 2-1 league defeat by Wovlerhampton Wanderers on February 5 and the England captain has not played since.
United are four points clear of second-placed Arsenal, who have a game in hand, while sixth-placed Liverpool are a massive 21 points off the pace, but still harbour ambitions of qualifying for the Champions League.
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