Erik ten Hag and his players are back in European action after a three-month hiatus, and Xavi's La Liga leaders are the opposition.
The teams go head to head in Catalonia at 17:45 GMT on Thursday, with the return match taking place at Old Trafford seven days later.
Casemiro is part of the group travelling over to Spain, as the Brazilian is available for this fixture despite still being banned in domestic competition following his red card against Crystal Palace.
Lisandro Martinez and Marcel Sabitzer are suspended though, having each picked up three bookings in Europe before the turn of the year - Sabitzer's yellows carry over from his participation in the Champions League group stages with Bayern Munich.