United go into the clash with the Spanish side following a morale boosting win over the Reds that put them in pole position to secure second position in the English Premier League behind Manchester City.
Manchester United's 2-1 win over Jurgen Klopp's side gave them a five point cushion in second place and further bolstered the feel-good factor at Old Trafford following a hard February.
Marcos Rojo, Phil Jones, Ander Herrera and Daley Blind were others absent, although Anthony Martial and Zlatan Ibrahimovic trained ahead of the game.
But some fans and pundits are not happy with the style of football Jose Mourinho is playing at Old Trafford. "I don't feel we have any advantage at the moment. So, of course, knockout becomes more important than league matches".
"I remember at the beginning when I was taking him as an extra player, in the meetings, in the dressing room at half-time eating every word, listening to everything", Mourinho told reporters.
Sevilla last reached the quarter-finals of Europe's top competition in 1958, only the third edition of the European Cup, losing to eventual winners Real Madrid.
"We need to score one goal", said the 43-year-old in his pre-match conference.