Wayne Rooney, Anthony Martial and Marouane Fellaini are all fit to return to the squad, but Phil Jones and Ander Herrera are out after picking up knocks at Watford.
Antonio Valencia and Michael Carrick remain sidelined, whilst Luke Shaw will have a scan on Friday to see how his leg is recovering following the horrific injury sustained in the reverse fixture in September.
Bastian Schweinsteger missed training on Tuesday, but Louis van Gaal explained that he had given the German a rest day and that he should be available for the Old Trafford encounter.
Addressing the media on Tuesday, van Gaal said that his side have "learned lessons" from that 2-1 defeat in Holland on Matchday 1.
"I remember that the last match against PSV was not a good one for us- not only because of the result but also because of the loss of Luke Shaw.
"For us, the most important lesson is that we have to move the ball quicker and we created a lot of possibilities to score but did not take them, so this is something that you can always improve and I think we have showed that."
Philip Cocu's PSV side come to Old Trafford sitting third in the Eredivisie, behind perennial rivals Ajax and Feyenoord whilst their Champions League form has been inconsistent so far.
They have lost both of their away matches in Group B so far (3-2 in Moscow and 2-0 in Wolfsburg) and their 2-0 home win over the Germans last time out was their first since that victory over us in the opening round of matches.
In contrast, United have won both matches on home turf and know that similar success on Wednesday will secure a passage into the knockout stages with a game to spare.
Van Gaal added:
"If we beat PSV then we have qualified and that is our goal of course, it is very important to win but it shall not be easy because every game you have to play you cannot say in advance that you will win.
"PSV beat Manchester United last time and they also beat Wolfsburg so I think that they are a very good team."
"I'm very happy because Rooney is recovered and Martial can play, Fellaini also so that is great news I think."
Form guide: United D D D W W W PSV L W W W W D
Match odds: United 15/7 Draw 39/11 PSV 31/5Referee: Pavel Kralovec (Czech Republic)
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