Manchester United go to FA Cup opponents Cambridge United tonight without defenders Chris Smalling and Jonny Evans.
Evans limped out of last weekend's win at Queens Park Rangers while Smalling is understood to have picked up an injury in training.
"It's always tough to play against teams who are weaker in the players' minds," Van Gaal said. "For example, on Wednesday PSV Eindhoven, the No.1 team in the Netherlands lost against the No.3 of the second division (Roda JC). It shall happen also in the FA Cup. There are always surprises and I hope that we are not the surprise.
"We prepare the same way and of course it's maybe in another way because in our minds you believe that we are playing a weaker opponent but it's not like that. It's another opponent with another playing style, and if you lose the game you are out."
