City proved far too good for their hosts in the first leg two weeks ago, winning 3-1 in impressive style at Old Trafford.
Pep Guardiola says the game is still very much there for Ole Gunnar Solskjaer's side but it will take something extraordinary to knock City out at this point.
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"We're a little bit lighter but we can't just defend we have to go out there, try and keep the ball as well which isn't too easy because they're good at pressing so it needs to be perfect," said Solskjaer.
Here's everything you need to know:
Predicted line-ups
Manchester City: Ederson, Walker, Stones, Fernandinho, Mendy, De Bruyne, Rodri, Gundogan, Bernardo, Jesus, Sterling
Manchester United: De Gea, Wan-Bissaka, Lindelof, Maguire, Williams; Fred, Matic, Greenwood, Periera, James, Martial
Team news
Marcus Rashford and Scott McTominay remain absent for United, as does Paul Pogba. Nemanja Matic is a doubt.
Kyle Walker and Raheem Sterling could return to the City line-up, while Joao Cancelo and Riyad Mahrez are nursing knocks and may not be involved.
Odds
Manchester City 1/3
Draw 21/4
Manchester United 17/2
Prediction
City are just too good for this United team. City 1-0 United.
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