Manchester City are in control after a demolition derby in the first leg 22 days ago, the Citizens had three goal first half lead over at Old Trafford.
Bernardo Silva, Riyad Mahrez and an own goal from Andreas Pereira, In the second half, Marcus Rashford did pull one back for Man United.
They did win at the Etihad last month but will need to pull a comeback to leave victorious this time.
Last time out in the Premier League, Sergio Agüero scored the only goal of the game as they thrashed Sheffield United at Bramall Lane. They have taken 19 points from their eight league matches since losing to Man United on 7 December, scoring 21 goals in that time.
They are 16 points behind league leaders Liverpool who have a game in hand which is at West Ham also on Wednesday.
On Sunday they’ll face Fulham in the FA Cup at home .
Manchester City team news
First choice goalkeeper Ederson is expected to be rested with Claudio Bravo stepping up from the weekend.
20 of Bravo’s 27 appearances since the start of the 2017/18 season have been in cup competitions.
João Cancelo could keep his place over Kyle Walker at right-back. Oleksandr Zinchenko is likely to return with Benjamin Mendy rested.
Aymeric Laporte made his long awaited return at Bramall Lane last midweek but Eric García could be given another opportunity.
John Stones could come in with Nicolás Otamendi rotated out and Rodri could return for this match. Phil Foden is highly likely to get another start.
Bernardo Silva will keep his place but David Silva will be rested. Raheem Sterling could return with Riyad Mahrez on the other side.
Gabriel Jesus bagged a late brace against Fulham, Sergio Agüero is likely to be rotated back in.
Manchester United team news
Sergio Romero has started all three of his month’s FA Cup ties but David de Gea is likely to keep goal for this one.
They went with a back five at the weekend. Aaron Wan-Bissaka returning at right-back. Brandon Williams will return in place of Luke Shaw.
Phil Jones was another scorer at Tranmere but it’ll be the usual partnership of Harry Maguire and Victor Lindelöf for this one.
There’s still no Paul Pogba or Scott McTominay.
Nemanja Matić will keep his place with Fred displacing Andreas Pereira.
Jesse Lingard scored his first goal for one year and one day last time out but will likely benched with Dan James and Juan Mata returning.
Mason Greenwood and Anthony Martial will make up the attack with Marcus Rashford ruled out until April.