Preview: Unusual edge to Manchester derby
United, of course, are not out of the Premier League title running but even victory at Eastlands would still leave Chelsea strong favourites for the silverware.
City desperately need the points to tighten their grip on the fourth place that secures a foothold on the Champions League.
United were in pole position three weeks ago but home defeat by Chelsea followed by a 0-0 draw at Blackburn Rovers has left them four points behind the Londoners with four games remaining.
It is not an insurmountable gap, even with Chelsea's recent big wins giving them a five-superior goal difference, but the bigger issue for United could now be holding off Arsenal for second place.
Arsene Wenger's side are third, two points behind, after their 2-1 defeat at Tottenham Hotspur on Wednesday.
City are fourth on 62 points, one ahead of Spurs, who next face Chelsea and Manchester United.
Liverpool, on 56 and Aston Villa, on 55 after their 2-2 draw with Everton on Wednesday, are also still in the hunt for fourth but it is very much City's to lose.
Saturday's game is the fourth Manchester derby of the season and will have to go some to live up to the previous three.
United won the Old Trafford league clash 4-3 in September as Craig Bellamy's brilliant last-minute equaliser was trumped by Michael Owen's stoppage-time winner.
City won the first leg of their League Cup semi-final 2-1 with a double from former United forward Carlos Tevez, only for United to snatch a place in the final with Wayne Rooney's last-gasp goal for a 3-1 Old Trafford success in the second leg.
The England striker remains a doubt for Saturday through a twisted ankle that kept him out of the Chelsea and Blackburn games.
United fans, unimpressed by the efforts of Dimitar Berbatov in Rooney's absence, will be desperate to have him back and they found an unlikely ally this week in the form of City manager Roberto Mancini.
"I think it is better if Rooney plays on Saturday," he told the club's website.
"He is a fantastic player and has had an amazing season. He will be a danger, of course, but United have many fine players in their team -- but we have beaten them once at home already and can do it again.
"I think it's best if both teams are full strength and then the side who takes the three points can truly say the best team won and there is no reason that cannot be us."
City are certainly the form team going into the game, having won three league games in a row and scored 14 goals in the process.
"We've gelled as a squad at the right time and we're hitting the right notes just when we need to," said midfielder Gareth Barry. "We're finishing the season strongly."
United's Ryan Giggs is hoping to recover from a hamstring strain in time to play on Saturday, maintaining his remarkable record of never missing a derby since he began playing in 1991.