Chelsea have not tasted victory at United in the Premier League since Juan Mata's late winner in May 2013, while the fixture holds the unwelcome distinction of being the most drawn encounter in Premier League history with 27 stalemates.
While fifth-placed Chelsea are hoping to extend their unbeaten league start to five games, United are 14th with one win but Maresca is wary of the threat posed by Ruben Amorim's side who are smarting from their 3-0 weekend derby defeat.
"It's always difficult to play United away at Old Trafford. Now is not the right moment, next year or last year, it's always difficult," Maresca told reporters ahead of Saturday's game.
"Some of the games they have played this season are not the real result. Even the Man City game, until 1-0, 2-0 they were in the game. At 0-0 they had a few chances to score. It will be a tough game, no doubt.
"When you struggle, there's a desire to win the next game. Against Chelsea, at home, in front of their fans, they are all reasons why this game is important for them."
One Chelsea player who knows Old Trafford well is Alejandro Garnacho and Maresca said the 40 million pounds ($54 million) signing is ready to start after coming off the bench in their previous two matches.
"In the last two games, he was very good when he came on. We're happy with the way he's adapting to our style and what we want from the winger. I think he is ready to start," Maresca said.
Garnacho also has a point to prove after the Argentine was one of five players frozen out of Amorim's squad before his departure and Maresca said the player would have to keep his emotions in check if United fans give him a tough time.
"It's always difficult... But you have to learn to handle these things," Maresca added.
He also said Cole Palmer is available despite the England international holding his groin in Wednesday's Champions League loss to Bayern Munich. Palmer made his first start after a groin injury and scored in the 3-1 defeat.
"Cole is okay. We have a session now, we flew back yesterday (Thursday). We need to assess some players, we have some doubts," Maresca said. "We didn't have a session since Wednesday's game, but we will see."