The Blues have two wins from their opening three matches and will be looking to bounce back from their defeat at Reading at the end of August.
United have won just the one match so far, their season opener against Leicester, and a loss at Southampton and draw with Chelsea mean the Reds have four points so far.
Simon Davies' side beat United 1-0 when they last met at the Etihad Stadium in February but where will Friday evening's match be decided?
Nmecha v Johnstone
City have been exciting so far, scoring six goals in their three matches. Striker Lukas Nmecha is perhaps the Blues' most lethal goal threat.
The 17-year-old scored a brace in the opening weekend comeback at Derby County to get the Blues season off to a flyer and continue his impressive form after winning the Golden Boot at the pre-season RUHR Cup win.
He will have to beat ex-England U21 ‘keeper Sam Johnstone if he is to add to his tally on Friday evening. Johnstone, now 23, spent last season on loan at Championship club Preston North End and his experience is vital behind United’s young defence.
Nmecha is known for his remarkable composure in scoring positions and if sent through on a one-on-one with the domineering Johnstone, it will be an interesting battle between two players comfortable with that scenario.
Kongolo v Harrop
City midfielder Rodney Kongolo is renowned for his tirelessness but the box-to-box midfielder is also a clever footballer, often timing his runs past opposition midfielders to perfection in order to arrive at the perfect moment.
The best example of that so far this season was his winner against Arsenal when Aaron Nemane’s cross found Kongolo who swept home from the edge of the box.
His battle with United’s Josh Harrop could have a large impact on which side dominates possession of the ball. Harrop is a creative midfielder but he certainly won’t avoid a challenge.
Whoever can come out on top in the centre of the Etihad Stadium pitch is likely to be able to set the tone of the evening.
There will be plenty to look out for throughout the Premier League 2 derby. Visit the ticket office for information on how you can support our future.