A win or draw would do for City, who trail Arsenal by a single point. United, however, would have to win by four goals to go top on goal difference. That, obviously, will not happen.
Bastian Schweinsteiger was substituted at half-time in the match against CSKA Moscow, to be replaced by Marouane Fellaini, but if Schweinsteiger does not start then he could be replaced by Michael Carrick. Morgan Schneiderlin and Ander Herrera are likely to complete the midfield line up.
Captain Wayne Rooney will keep his place despite being the worst player in the Premier League at the moment, but he might be asked to take on the same role as in the last derby, when he made sure to press the two central defenders, which he is better able to do than run, pass, control the ball, or have a positive impact on the team in any other way.
Daley Blind and Matteo Darmian could replace the poor Marcos Rojo and Antonio Valencia, respectively, but the central defensive pairing of Chris Smalling and Phil Jones is unlikely to be changed.
You can read Jack Sargeant's excellent match preview here.
When: 2.05pm GMT, 9.05am ET.
Where: Old Trafford, Manchester
How to watch: Sky Sports 1 for UK, NBC for US.
How to watch online: Sky Go for UK, NBC online for US.