United head to St Mary's to fulfill their penultimate fixture in the Premier League at a time, when all thoughts are directed towards next Wednesday's Europa League final. Sunday's 2-1 loss to Tottenham at White Hart Lane ensured that United will finish outside the top four for the second successive season - for the first time since 1989/90 and 1990/91 - but they do still have the opportunity to qualify for the Champions League by beating Ajax in Stockholm next week.
However, Claude Puel and his side will not be ready to go lightly on what ever side Mourinho puts out, and after back-to-back league defeats there is an onus on United to deliver a performance.
MAN UTD INJURIES
Zlatan Ibrahimovic has returned from America after successful surgery on his ACL damage and now faces the beginning of a long process of rehabilitation, while Marcos Rojo is in a similar boat after sustaining exactly the same injury in the same match against Anderlecht in April.
Luke Shaw is also out for the remainder of the season with a foot injury as is Ashley Young with a hamstring pull, while Timo Fosu-Mensah's shoulder problem again keeps him on the sidelines.
MAN UTD SUSPENSIONS
Marouane Fellaini returns to domestic contention after serving a three-match ban following his sending-off at Manchester City in April. The big Belgian elbowed Sergio Aguero in the derby draw to earn a red card, but is back in the squad after missing the games against Swansea City, Arsenal and Tottenham.
MAN UTD POTENTIAL STARTING LINE-UP
Mourinho will again make changes as he freshens up his squad ahead of next week's Europa League final, and David de Gea will not take part in Southampton after being left out of the travelling party. Sergio Romero will start in goal for only the second time this season in the league.
Elsewhere, Antonio Valencia and Daley Blind were also not included on the trip south, meaning Axel Tuanzebe and Matteo Darmian are on standby for potential starts, with left-back Demi Mitchell another possible option.
There is no Paul Pogba as he continues to spend time with his family following the death of his father last Friday. Mourinho explained that the midfielder will stay in France until after the funeral, meaning he could have played his last league action of the season.
Scott McTominay may be considered for a start after making his debut from the bench at Arsenal recently, while Fellaini will come back in having only played two European games in the last three weeks. Further upfield, Marcus Rashford could be given a run-out to keep him in shape ahead of the trip to Stockholm next week.
SOUTHAMPTON TEAM NEWS
Puel's side have found it hard to reproduce the form of recent seasons in 2016-17, although February's appearance in the EFL Cup final did at least give them their first taste of a showpiece occasion since the 2003 FA Cup final loss to Arsenal.
Since that 3-2 loss to United at Wembley, the Saints have continued to be inconsistent. The 2-1 win at Middlesbrough last time out ended a five-game run without a win, although the 0-0 draw with relegated Hull City was arguably the only one of real disappointment since the other games saw them take on Manchester City, Chelsea, Arsenal and Liverpool.
Manolo Gabbiadini, who netted both of Saints' goals in the EFL Cup final, remains their biggest threat in the final third despite having not scored in two months. The striker admitted in an interview this week that he hopes he can go on a run of form with Southampton which will lead to him being called up by Giampiero Ventura for the Italy World Cup squad next summer.
BEST OPTA MATCH FACTS
Manchester United’s last away defeat in the Premier League to Southampton came in August 2003, with James Beattie scoring the only goal of the game.
- Four of Manchester United’s five goals against Southampton in all competitions this season have been scored by Zlatan Ibrahimovic, who has been ruled out for the season.
- Manchester United have come from behind to beat Southampton on eight occasions in the Premier League (including in this exact fixture last season) – the most any team has done so against another in the competition’s history.
- Southampton have failed to score in their last three home league games, with their goalless drought at St Mary’s currently standing at four hours 35 minutes. They’ve never gone four top-flight home games without a goal.
- Manchester United haven’t lost three Premier League games in a row (or in a single month) since December 2015 under Louis Van Gaal.
- Jose Mourinho’s side have won more points away from home this season in the Premier League (34 in 18 games) than they have at Old Trafford (31 in 18 games).
- Manchester United (17 wins) need to win both of their remaining Premier League games in 2016-17 to avoid it being their lowest tally of wins in a single Premier League season. They won 19 in both 2013-14 and 2015-16.
TV COVERAGE & KICK-OFF TIME
The game at St Mary's kicks off at 19:45 UK time, with live television coverage on Sky Sports 1 in the UK.