Ryan Giggs will be in interim control for the trip to the South Coast, but it is seemingly only a matter of time until outgoing Netherlands boss Louis van Gaal is announced as United manager for next term.
Giggs has confirmed this week that he will continue his playing career into his 41st year, but the win over Hull City on Wednesday also proved that the Welshman has an eye on the long-term future of the club.
Teenage striker James Wilson scored twice on his Premier League debut, and a couple of Saints stars could be playing alongside him at Old Trafford next season as part of a new-look Red Devils squad.
While the prospect of a £200m war chest has United fans excited for the upcoming transfer window, Southampton supporters will head into the summer with trepidation over the potential snaring of the club's best players, and also their manager, Mauricio Pochettino, who is interesting Tottenham Hotspur.
The Argentine will be without Gaston Ramirez, Maya Yoshida and Kelvin Davis for their season finale, while Jay Rodriguez remains out with the cruciate knee ligament injury that has cost him a World Cup place.
As well as frontman Rickie Lambert, Lallana and Shaw could both make the plane to Brazil, and the Saints faithful will be hopeful that it is not the last time that they see them in their colours.
There are sure to be some goodbyes in the United ranks, with Nemanja Vidic having already agreed to join Inter Milan and Rio Ferdinand and Patrice Evra other experienced defenders who could be leaving.
Phil Jones is being tipped to be the future of the Old Trafford back line, but he will not feature this weekend after limping off in midweek. Giggs, however, is predicting that he will be fit for Brazil next month.
Wayne Rooney is another who will not be chanced, so Wilson will maintain his place up front alongside Robin van Persie, who could be handed his first start since scoring a hat-trick against Olympiacos on March 19.
United could qualify for the Europa League if they win and Tottenham lose at home to Aston Villa.
Man United: WLWLWW
Possible starting lineups
Southampton: Boruc; Clyne, Fonte, Lovren, Shaw; Schneiderlin, Cork, Davis, Ward-Prowse, Lallana, Lambert
United: De Gea; Smalling, Ferdinand, Vidic, Evra; Valencia, Carrick, Fellaini, Januzaj; Van Persie, Wilson
Sports Mole says: 1-1