United must make a 1,600-mile journey back from Moscow after the 1-1 draw with CSKA in the Champions League, putting the team at a disadvantage ahead of the derby, according to Van Gaal.
"Manchester City don't have the travel we have so they have more rest," Van Gaal said. "There is nothing you can do. They have the benefit."
United is in mixed form heading into the weekend, having lost 3-0 to Arsenal and won 3-0 at Everton in its last two Premier League games.