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Virgil van Dijk could make his first start for Southampton since January, having returned to competitive action as a substitute last weekend.
He will be assessed after playing for the U23 side on Monday but Matt Targett is a doubt due to an ankle injury.
Manchester United have no fresh injury worries with Marcus Rashford and Anthony Martial pushing their claims for a starting role by scoring in the League Cup win over Burton.
Jonathan Pearce: "Every time I climb up to the St Mary’s gantry a Saints fan asks me: ‘Will we be okay this season?’. I’ve always reassured him. In all honesty I can’t do so right now.
"Any side that has scored just one home goal from free play in 725 minutes, with eight home scoring blanks in nine matches, is bound to find trouble. They have to get Charlie Austin fully fit and firing.
"Manchester United look far too strong for them. They average three goals a game. Romelu Lukaku alone has more than the whole Southampton side. Jose Mourinho looks like the cat that got the cream.
“It’s 14 years since a Saints home win in this fixture. I can’t see that hoodoo being broken.”
Southampton manager Mauricio Pellegrino: "When we play against the biggest team in the world, it allows us to draw some conclusions about how we are.
"This is for me the nice challenge and we have to strive for this.
“Playing against Manchester United is one of the most beautiful things. I will live this opportunity, I will live this game, and now we have to try to enjoy this game.”
Manchester United manager Jose Mourinho: "Southampton is the kind of club that are very stable in the way they play and in the way they see football, the qualities of their players…
“I see the match tomorrow as a very difficult match.”
I am expecting United to dominate this game and create lots of chances. Eventually they will find a way through.
SAM (Sports Analytics Machine) is a super-computer created by @ProfIanMcHale at the University of Liverpool that is used to predict the outcome of football matches.
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