The Reds will go 19 points ahead of their arch rivals with victory, with three points also seeing them regain top spot in the Premier League table.
The manager has made four changes to the side that beat Napoli during the week to progress to the last 16 of the Champions League.
Substitutes: Mignolet, Henderson, Sturridge, Moreno, Lallana, Shaqiri, Camacho.
Man United: De Gea, Darmian, Smalling, Lindelof, Dalot, Young, Matic, Herrera, Lingard, Lukaku, Rashford.
Substitutes: Romero, Bailly, Valencia, Mata, Martial, Pogba, Fellaini.