The Black Cats are still chasing their first Premier League win of the season having claimed only one point from their opening six fixtures, while United have suffered back-to-back league defeats.
David Moyes' side were in Champions League action during the week and Giaccherini believes that this could work to Sunderland's benefit who will again be managed by caretaker boss Kevin Ball.
"They are the champions and it would be a very difficult game for us whenever we played them," he told the Sun.
"But they drew 1-1 against Shakhtar Donetsk on Wednesday and Ukraine is a long way to travel. That can affect you in the next game.
"I saw this at Juventus, where we played in the Champions League in the week and then three days later we were playing in the league. It is not easy and they have also not started as well as they wanted.
"I watched their game against West Brom last weekend on the TV. It is not often that a big team loses two games in a row.
"If we could win against Manchester United, or even draw, it would give everyone a lot of confidence."