After a 0-0 draw at the Estadio Ramón Sánchez Pizjuán last-month, the LaLiga side will be buoyed knowing an away goal could prove to be the vital difference on Tuesday evening.
However, Los Rojiblancos have yet to taste victory in the Champions League on English soil in seven attempts and they come up against a defensively resolute Red Devils outfit.
United are brimming with confidence following their impressive 2-1 North West Derby victory over Liverpool on Saturday and will look towards the fixture against Vincenzo Montella's side as a way to create further momentum in the final stretch of the season.
Mourinho will be without defenders Phil Jones, Marcos Rojo and Daley Blind, and midfielder Ander Herrera.
Manchester United: De Gea, Valencia, Bailly, Smalling, Young, Matic, Fellaini, Lingard, Sanchez, Lukaku, Rashford
Sevilla: Rico, Mercado, Kjaer, Lenglet, Escudero, N'Zonzi, Banega, Vazquez, Sarabia, Muriel, Correa