With United not playing until facing Tottenham in a tricky away game on Sunday, Roberto Mancini's men can make a statement by winning at the Etihad Stadium a day earlier.
A positive result would cut the deficit at the top to four points and put pressure on United to respond.
A number of City players have spoken in recent weeks of the need to be ready to pounce should United slip up, with playmaker David Silva urging his team-mates to "keep going, every game".
Midfielder Javi Garcia, who could have a crucial role to play in the continued absence of Yaya Toure over the next month, is also keen to take the fight to United.
The Spaniard, who is still to fully establish himself at City following his £15.8million move from Benfica last August, said: "We need to fight until the final (game) with them.
"I think the team worked very hard (last week) and we were very happy."
City must continue to make light of the unavailability of midfield inspiration Toure, who is on African Nations Cup duty with Ivory Coast along with brother Kolo.
The Toures were badly missed during last season's tournament, with City going out of both domestic cup competitions and losing a crucial league game at Everton during their time away.
City were lifted this week as captain Vincent Kompany succeeded in his appeal against the red card he received in the latter stages at the Emirates Stadium.
A ban which would have significantly weakened Mancini's defensive options further with Kolo Toure away.
City are also hoping Sergio Aguero, who tore a hamstring in the New Year's Day win over Stoke might be fit to return while Samir Nasri is available after his suspension.
Mancini's side should also be fresher than Fulham having not been involved in midweek action.
The Londoners were taken to extra time in freezing conditions at Championship side Blackpool in an FA Cup third-round replay on Tuesday.