The Reds will be strong favourites to progress to the round of 16, having secured a convincing 4-0 win in last week's opening game.
Here's everything you need to know about the return of European football to Old Trafford...
MATCH DETAILS
Despite last Thursday’s opening leg taking place in Turin, rather than San Sebastian, due to travel restrictions imposed by the Spanish government, this game will be played in Manchester. As with all knock-out games in European competition in 2020/21, the tie is being contested over two legs and includes VAR and the away-goals rule, which is applicable if the teams are level on aggregate after 180 minutes.