Van Persie sustained an ankle injury in the defeat at Swansea last month and sits out the visit of fellow top-four chaser Spurs,
Louis van Gaal revealed Marcos Rojo is a minor doubt due to a knock the defender picked up in the FA Cup defeat to Arsenal on Monday night.
Jonny Evans and Angel Di Maria miss out due to suspension.
Tottenham head coach Mauricio Pochettino has a fully-fit squad to choose from.
With only league fixtures remaining, Pochettino has been able to give his squad a two-day break in the lead up to the game at Old Trafford.
Emmanuel Adebayor, Younes Kaboul and Etienne Capoue will be hoping to be included in some capacity having not been involved in a matchday squad since January.