United manager David Moyes told reporters on Tuesday that Van Persie was still nursing a groin injury that had ruled him out of the Netherlands' internationals earlier this month.
"Robin is not quite ready yet," Moyes said. "It's not long-term, but we're going to keep monitoring him."
Serbia defender Vidic suffered concussion in a Premier League match against Arsenal earlier this month and has also been ruled out of the Leverkusen game.
Both players missed the 2-2 draw at Cardiff City on Sunday.
United will book a place in the last 16 with a victory in Germany. They are top of Group A with eight points, one ahead of Leverkusen with two games left to play.
"We have to make sure we're defensively sound and also that we go out there to win the game," said the Scot.
Ukraine's Shakhtar are third in the group on five points with Real Sociedad trailing in last place with one point.
(Reporting by Karolos Grohmann; Editing by Ken Ferris)
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