Both sides of the Manchester divide will be hoping some derby delight can add impetus to disappointing seasons when City host United on Saturday, while Liverpool travel to Bournemouth aiming to surge further clear at the top of the Premier League.
Manchester United got a badly needed win for manager Ole Gunnar Solskjaer on Wednesday, inflicting a first defeat as Tottenham manager on Jose Mourinho as the Portuguese returned to Old Trafford.
The Red Devils were again reliant on Marcus Rashford goals as the England forward struck twice to take his tally to 12 in 13 games for club and country.
"He was strong, direct, taking people on, inside and outside with no fear," said Solskjaer.
"That's what we want -- we want to see boys enjoying themselves." There has been precious little for United fans to enjoy this season, but just a fifth Premier League victory in 15 games was enough to lift them up to sixth.
That is still 11 points adrift of third-placed City, despite their own struggles at times.
Pep Guardiola's men looked more like their old selves in thrashing Burnley 4-1 on Tuesday with Gabriel Jesus stepping up in the absence of the injured Sergio Aguero to score twice.
City have lost just one of six league meetings with United since Guardiola took charge three years ago and cannot afford to slip up if they are to maintain any aspirations of catching Liverpool in the title race.
The English champions could kick-off at the Etihad 14 points behind the leaders, should Jurgen Klopp's men continue their scintillating form at Bournemouth earlier on Saturday.
"For the distance we are behind Liverpool it would be crazy to think about the title, we have to think about the derby," said Guardiola.
- Strength in depth -
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Klopp could even afford the luxury of leaving Roberto Firmino and Mohamed Salah on the bench for a 5-2 thrashing of Everton in the Merseyside derby in midweek.
Both are expected to return for the visit to the south coast, but Klopp may rest some of his stars who did start against Everton ahead of a huge week for the European champions.
Liverpool travel to Salzburg in the Champions League on Tuesday needing to avoid defeat if their defence of the title is not to embarrassingly end in the group stages.
Divock Origi scored twice against Everton and Xherdan Shaqiri struck on his first start of the season to prove Klopp does have the strength in depth to successfully shuffle his pack.
"It's easy for me to tell them often, very often, how good they are but if they then don't play it's not too easy for them to always understand what I say," said Klopp.
"But if they play and deliver like they did, it's a very, very important sign for the whole squad."
- Leicester aiming for cloud nine -
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Leicester remain Liverpool's closest challengers, eight points back in second, thanks to a run of eight straight wins in all competitions.
"The team is developing and are proving they have a winning mentality and mindset," said Leicester boss Brendan Rodgers, who has dismissed speculation linking him with the vacant managerial role at Arsenal.
Next up for the in-form Foxes is a trip to Aston Villa on Sunday.
Villa are one of a host of teams hauled back into the battle to avoid relegation by Southampton's resurgence with Dean Smith's men just one point above the drop zone.
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