Midfielders
Nemanja Matic, Paul Pogba and Fellaini
Mourinho has consistently played three in midfield this season, and he is unlikely to change that at least until January.
Southampton's players are very physical, so Mourinho will want to counter that with his own set of giants. This is likely to destabilize the creative aspect of Manchester United, but that will not bother the Portuguese in any manner.
Pobga only played 25 minutes against Young Boys, so he should be fit. He is a game changer and on a good day, he can dictate the play.
Matic on the other hand needs a rest but Mourinho is unlikely to allow him that as he needs his team to regain momentum. The Serb is one of Mourinho's favourite players, and plays according to the manager's script.
Fellaini scored the winning goal in the Champions League and is a typical Mourinho kind of player. His aerial prowess and ball retention capability will be crucial in hostile territory.