Defender Ferdinand has not recovered from the back injury which forced him to miss last weekend's home game against Stoke and England's midweek international friendly win against Germany in Berlin.
"Rio is very doubtful for tomorrow, I don't think he'll make it," United boss Sir Alex Ferguson told the press on Friday.
Elsewhere, Wayne Rooney could feature in Saturday's clash at Villa Park as he has resumed training this week having been sidelined with a chest infection and calf injury.
"Rooney has a good chance, he trained on Wednesday and Thursday and if he comes through today he should be involved," Fergie added.