Van Persie was a surprise absentee from the United team that was thrashed 4-1 by Manchester City on Sunday and it was revealed later he was struggling with a groin injury.
Boss David Moyes addressed the Van Persie question at his press conference before the Old Trafford clash, the highlight of the third round ties.
He said: "I don't think he will play on Wednesday. He will have an outside chance for Saturday (home to West Brom)."
Moyes admitted Wednesday's game takes on added significance - if it was needed - on the back of their heavy defeat at the Etihad Stadium and although changes are likely, they might not mean the inclusion of too many young players.
"It (Sunday) has gone now," he said. "I can't do anything about it. We have moved on and we get ready for the next game.
"When you have been a football manager for the amount of time I have you are always going to have shocks.
"I have had lots and I have no doubt there will be more in the future. That is the way football is."
The game also marks the return of Liverpool striker Luis Suarez after a 10-match ban for biting Chelsea defender Branislav Ivanovic, but Moyes would not be drawn on his return.
"It means Liverpool have got a really good player," said Moyes. "Does it change the complexion (of the game)? I am not looking at Liverpool too much. I just know the qualities of Luis Suarez are very good."
You can watch Manchester United take on Liverpool in the third round of the Carling Cup live on Sky Sports 1HD, with the programme starting at 19:00