United will be looking to end a difficult week on a high with a trip to Southampton, a fixture that has yielded narrow victories in the last two seasons.
Ronald Koeman's side, who finished seventh last season- including a 1-0 win at Old Trafford- have made an indifferent start this time around with a win, a defeat, three draws and a European exit to Midtjylland.
Having said that, on their day they can be dangerous underdogs and with the quality of the likes of Jay Rodriguez, Victor Wanyama and Graziano Pelle, can pose a threat for the best of sides so the visitors will need to be on their mettle.
Luke Shaw's injury has overshadowed the past few days and denied him a return to St Mary's, but United manager Louis van Gaal has said that the full back's injury can "galvanise" his side.
Van Gaal added that United would dedicate a victory to their stricken team-mate, but, whilst Shaw is set for a long spell on the sidelines, Wayne Rooney is fit to play and Phil Jones could also feature having trained with the first team.
Marcos Rojo looks likely to come in at left-back for United's longest away trip of the season.
Speaking on Friday, Van Gaal said Shaw's injury was a "huge blow" but that there are "three options" to replace him with.
"I called Luke Shaw last night and he sounds very strong, which is amazing and a good sign.
"It is very difficult to change the left-back position, but we have three options- Blind, Rojo and Young- so we have good replacements.
"Southampton have a very good team, I don't think their current position is normal for them and they have shown the quality of their play so we have to be careful of them."
Form guide: Southampton L D D L W L United W D W L W L
Match odds: Southampton 7/4 Draw 2/1 United 6/4
Referee: Mark Clattenburg