Manuel Pellegrini's men came from a goal down to lift the League Cup trophy with a 3-1 win last month, but the result of Wednesday's Premier League fixture at the Etihad Stadium could have significant implications at both ends of the table.
City's 3-2 defeat at Anfield on Sunday left them seven points adrift of table-toppers Liverpool and five short of second-placed Chelsea.
The visit of Gus Poyet's bottom-placed Sunderland marks the first of two games in hand Pellegrini's side have over the leading pair, and they will be keen to put pressure on Liverpool against a team who have taken just one point from their last eight top-flight matches.
Edin Dzeko was part of the City squad that won the Premier League in 2012, and the Bosnian has refused to concede defeat in the race for this year's crown.
"It's too early to say if Sunday's result will decide where the title ends up because we still have six games to play and Liverpool and Chelsea both have four left," he told the club's official website.
"People talk about pressure and suchlike but that doesn’t really matter - just who wins the most games between now and the end of the season.
"We have to get back on track by beating Sunderland and West Brom in the next week."
Wednesday's match is just as important for the visitors, with Sunderland seven points adrift of safety, although they hold two games in hand over 17th-placed Norwich City.
Wins for Cardiff City and Fulham over the weekend have not helped the Wearsiders' cause, but midfielder Lee Cattermole has not given up hope of survival, with Sunderland likely to take confidence from their 1-0 triumph over City in November's reverse fixture.
"It's getting harder, but while there are points to play for, we can do it," he is quoted as saying by the Daily Express.
"You can't write off games like Manchester City and Chelsea coming up next because teams have been there in the past and won, but if we are to stay up we have to start picking points up now.
"We'll keep going and that's the type of performance we will demand from each other."
City are likely to be without Yaya Toure, who limped off at Liverpool with an apparent groin injury, but Sergio Aguero could be in line for a first start in more than a month after coming off the bench on Merseyside.
Sunderland striker Steven Fletcher faces the prospect of being relegated from the top flight with a third club, having already fallen through the trap door with Burnley and Wolves, but is highly doubtful to feature on Wednesday as he continues to suffer with an ankle problem.
The visitors are also without the suspended Phil Bardsley.
