The Red Devils have not always been at their best this term but have been perfect on their travels, seeing off Brighton & Hove Albion, Newcastle United and Everton.
Here, Sports Mole looks at how United could line up against in-form Southampton.
Victor Lindelof sustained a knock against Basaksehir and fellow centre-back Eric Bailly is already nursing an injury, so Axel Tuanzebe may come in for a first league start of 2020-21.
An impressive performance from Donny van de Beek will do his chances of finally starting in the Premier League no harm, but it is more likely that Nemanja Matic and Scott McTominay will get the nod here.
Fred is another option in that position, but Paul Pogba is unlikely to play any part because of a troublesome ankle issue.
Solskjaer has a big call to make up top given the disappointing form of Anthony Martial, who has failed to score or assist in any of his side's last five matches.
Influential playmaker Bruno Fernandes seems certain to start, meanwhile, having been involved in more Premier League goals than any other player since his debut in February (14 goals, 10 assists).
Watch the Sports Mole Football Shorts prediction for this game below: