Here, we take a look at the game's major talking points.
Everyone connected with City will has been stung by Wednesday’s night’s defeat at Anfield.
The key now is to translate that pain into fuel for success against United.
City’s performance this season has been, for the vast majority of the time, incredible and we have never lost two games in a row under Pep Guardiola.
Here’s hoping that record continues.
2Patience could be key
It would hardly be a surprise to see United play a defensive formation in a bid to nullify City’s wealth of attacking options.
And Jose Mourinho’s side have shown this season they are resolute defensively. They have the second-best defensive record in the Premier League, having conceded just 23 goals in their 31 matches so far.
Breaking them down won’t be easy and patience will be vital if we aren’t able to register an early goal.
City could clinch the title with more games to spare than any other side in English top-flight history, which, if it happens, would further underline our dominance this season.
And our home record suggests we can get the job done. We are unbeaten in our last 27 home league games (W22, D5), winning the last 14 in succession.
There can be little doubt that Pep has turned the Etihad into a fortress once again.
Guardiola and skipper Vincent Kompany have both reiterated how vital crowd support is – over the next two games, the Etihad Stadium faithful could prove the difference.
At this level, football is often a game of fine margins, and if the collective roar of around 50,000 City fans can translate into an extra one per cent from the players, it could be all important.