United will know that a win will see them go six points clear at the top, while City will be able to go level with their arch rivals if they get a win.
Both will have one eye on what’s happening behind them as Chelsea are desperate for a win and travel to a Sunderland team who are just waiting to turn in a good performance.
Tottenham travel to Everton on Sunday so there’s a possibility both could drop points – which again makes it even more important who wins the Manchester derby this weekend.
Crucially, both clubs will know how important a win will be in terms of morale.
Manchester City have just come off the back of a period which has seen them not only miss out on the next round of the Champions League but the Europa League too.
Bouncing back from that with a win will be a boost for the players but also for Roberto Mancini, because you feel all is not as it should be for the Italian at the moment.
On the other hand, Manchester United are comfortably through to the next round of the Champions League and are top of the Premier League but they are leaking goals in a way which is unlike United sides of old – getting a win at the Etihad will be a tough ask but you wouldn’t put it past Sir Alex Ferguson to get the best out of his players.
I imagine the thought of that 6-1 defeat still hurts United, especially someone like Ferguson, who is a very proud man – as he then watched City take away that title in such heartbreaking fashion.
I doubt they could replicate that same result against City this year but if Robin van Persie is on form and some of his team-mates can step up to the plate then United are going to score goals.
Both will have what happened at the end of last season in the back of their minds and I think that makes it for an even more fascinating contest than ever before.
If you look at both squads from top to bottom, City have more about them than United on paper. There are more match-winners across the squad and people who can stand up and be counted.
Home advantage will be massive for Mancini’s side – they are unbeaten there in so long that winning is just second nature to them on home soil and that makes them a formidable opponent.
People have been saying that, come March or April, he will think not playing in Europe will be a boost as he can focus solely on the league.
You could argue that, but you could also argue the opportunity to play fringe players in midweek and keep them fit and, most importantly, keep them happy will be something he will miss at that stage of the season.
There are pros and cons either way, but Mancini’s focus won’t be on March, or April, or May, it will be on 9 December.
Last season, a victory over United at home spurred them on to the title. The circumstances are different this year but it’s still just as important.
Andy Gray is an official ambassador for Sharethematch.com – Football’s Social Network. Available now for FREE online or at the App Store.
MORE: Man United latest news
MORE: Arsenal latest news
MORE: Chelsea latest news
MORE: Liverpool latest news