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Central Midfield: Michael Carrick and Marouane Fellaini
With Cleverley out of action and Anderson out of sorts, Carrick and Fellaini look to be Moyes' only realistic options in midfield.
Though as a partnership the pair lack pace and has looked rather pedestrian when called upon to take control of games, its defensive qualities could useful against Southampton's busy and intense approach to the game.
Fellaini will look to add a physical bite to the side, although the Belgian must ensure he doesn't give away too many fouls.
Meanwhile, fresh from receiving numerous plaudits for his considered and conservative performance as England's midfield anchor against Poland, Carrick will be set up to patrol the space ahead of defence, intercepting loose balls and preventing gaps from appearing in United's lines.
Wings: Danny Welbeck and Antonio Valencia
On the flanks, Welbeck could be deployed on the left, with his excellent work rate and link-up play a potential asset against the Saints' own hard-working wide men.
Based on their club form, Nani should get the nod from Moyes but, like Welbeck, Valencia's greater industry could see him selected to wear down Southampton's left-flank.
The Ecuadorian is another player coming back to the club after a fruitful international break. Having helped confirm his country's qualification that was dedicated to his late friend Chucho Benitez amid emotional scenes, he too may be given the chance to bring some of that impetus back to Manchester with him.
Kagawa, Ashley Young and Adnan Januzaj are other options, and with United's flanks currently one of the least convincing departments of the team, there's an argument to be made for any of the possible combinations to be involved.