The former full-back expects young Academy graduate Willy Kambwala to come into the team at centre-back, after Raphael Varane and Jonny Evans both picked up injuries against Chelsea on Thursday night.
Simpson is confident the youngster will rise to the occasion, too, predicting he will win the Man of the Match award this afternoon.
Our MUTV pundit also expects another goal-laden thriller in M16, with Alejandro Garnacho playing a key role.
After reading his forecasts below, you can enter your own in our United Predictions game. Will you agree with Simmo?
DANNY SIMPSON'S UNITED PREDICTIONS
Line-up: Onana, Dalot, Maguire, Kambwala, Wan-Bissaka, McTominay, Mainoo, Antony, Fernandes, Garnacho, Hojlund
First scorer: Alejandro Garnacho
Correct score: United 3 Liverpool 2
Man of the Match: Willy Kambwala
WHAT THE FANS ARE PREDICTING
First scorer predictions:
38% = Rasmus Hojlund
28% = Alejandro Garnacho
11% = Marcus Rashford
7% = Bruno Fernandes
5% = Antony
Correct score predictions:
29% = United 2 Liverpool 1
15% = United 3 Liverpool 2
8% = United 2 Liverpool 2
7% = United 3 Liverpool 1
5% = United 1 Liverpool 1
Man of the Match predictions:
26% = Alejandro Garnacho
16% = Kobbie Mainoo
15% = Bruno Fernandes
14% = Andre Onana
11% = Rasmus Hojlund
MUTV's live coverage of United v Liverpool begins at 14:25 BST.