The experienced defenders are to be rested for the European encounter but Ashley Young will feature as he has now fully recovered from a knee problem.
"I'm not playing Rio tomorrow," explained Sir Alex. "We have a game on Sunday against Chelsea and it’s a big one for us so I'm leaving a couple of players out. Rio and Patrice Evra are the older players – those are the two main changes for tomorrow. Other than that we’ve got a big squad.
"We've got Ashley Young back and he'll be involved tomorrow. We've got Nani, Valencia, Giggs... plenty of wide players. Of course, we also have plenty of central midfield players. So I have an issue in terms of picking the team. Hopefully I get it right.
"Shinji Kagawa didn't play on Saturday so he can prepare for tomorrow. Also, Stoke's a different team to any other side he's played. But mainly it was to give him a rest before tomorrow."
The manager was at pains to make clear that Ferdinand's exclusion was absolutely nothing to do with him refusing to wear a Kick It Out T-shirt before the Stoke City match.
"The issue's quite simple," he said. "I've spoken to Rio. I think there was a communication problem. He felt I should have spoken to him on Friday and I obviously didn't anticipate that he'd have a problem wearing the shirt.
"My advice to him was that I always feel a union is stronger than an individual. It's important he airs his grievances to the right people, to the PFA or the FA. It's been a communication problem rather than anything else.