Ole Gunnar Solskjaer will be without a host of key names due to injury - something he has chalked up to an increased workload in training.
Anthony Martial, Matteo Darmian, Phil Jones, Jesse Lingard, Juan Mata, Ander Herrera, Nemanja Matic and Antonio Valencia - the latter of whom the manager confirmed to be leaving the club at the end of the season - are all certain absentees or doubts one way or another.
However, Romelu Lukaku could see his showing against Crystal Palace rewarded with another start up front.
Potential Man Utd starting XI: De Gea; Young, Smalling, Lindelof, Shaw; Pogba, McTominay, Fred; Dalot, Lukaku, Sanchez.
With a 2-0 win over fellow bottom club Fulham helping to further boost their survival chances, Saints boss Ralph Hasenhuttl may be loathed to make any changes.
Mario Lemina remains an absentee with an abdominal problem.
Potential Southampton starting XI: Gunn; Bednarek, Yoshida, Vestergaard; Valery, Ward-Prowse, Romeu, Hojbjerg; Bertrand; Austin, Redmond.