The Red Devils have gone three games without success in all competitions, while collecting just two victories from their last five Premier League outings.
An untimely wobble has allowed the chasing pack to close in behind them, with Jose Mourinho’s side now just one point above third-placed Chelsea as the battle for top-four finishes intensifies.
MAN UTD INJURIES
Anthony Martial and Matteo Darmian have returned to full training to suggest that they will come back into contention against the Saints.
Chris Smalling is, however, still nursing a knock while fellow centre-half Eric Bailly is a long-term absentee after undergoing ankle surgery.
Antonio Valencia picked up a hamstring problem against West Brom prior to Christmas and has not been seen since, while Mourinho conceded heading into the festive period that Marouane Fellaini and Michael Carrick were unlikely to figure during a hectic run of games.
MAN UTD SUSPENSIONS
United have no players currently serving a suspension, with Marcos Rojo having escaped a ban despite accumulating five yellow cards.
The Argentine defender was cautioned early on in the Boxing Day draw with Burnley, but the first cut off point for the season came after 19 fixtures and a clash with the Clarets was the Red Devils’ 20th of the campaign.
POTENTIAL STARTING LINE-UP
Mourinho may decide to shuffle his pack once again as the games continue to come thick and fast.
Zlatan Ibrahimovic was played in a deep-lying No.10 role against Burnley, but he was replaced by Jesse Lingard at half-time and the England international went on to bag a brace.
Victor Lindelof is another who could come back in after spending the Clarets stalemate on the bench, while Martial could be handed an immediate recall and youngster Callum Gribbin a place among the substitutes.
SOUTHAMPTON TEAM NEWS
Virgil van Dijk will definitely not feature for the Saints following confirmation that a £75 million move to Liverpool will be pushed through on January 1.
Mauricio Pellegrino could also be without Charlie Austin after seeing the striker pick up a hamstring injury against Huddersfield, while Cedric Soares is nursing an ankle complaint and Ryan Bertrand is doubtful.
TV CHANNEL & KICK OFF TIME
The match takes place at 17:30 GMT on Saturday and will be shown live in the UK on BT Sport 1. Highlights can be caught on BBC's Match of the Day at 22:30.
In the United States (US), Manchester United v Southampton can be watched live and on-demand with fuboTV (7-day free trial).
BEST OPTA MATCH FACTS
The Red Devils have kept a clean sheet in each of their last three Premier League games against Southampton, after a run of nine games without one.
Southampton have won two of their last three league visits to Old Trafford, after a run of 19 games without a win there (D3 L16).
Southampton have won just one of their last 11 Premier League games (D4 L6) and none of the last seven. Indeed, Saints have failed to keep a clean sheet in each of those 11 matches.
Man Utd have lost just two of their 29 Premier League home games under Jose Mourinho (W16 D11 L2), with both defeats coming at the hands of Man City.
Man Utd have scored nine goals via substitutes in the Premier League this season – one more than in the previous two seasons combined (8).