City, who went top of the table with a crushing 5-1 win at Tottenham Hotspur on Wednesday, host Chelsea after Jose Mourinho's team were held 0-0 at home by West Ham United in a London derby on Wednesday.
The big clash at the Etihad, where City have scored 42 goals in 11 league wins this season, will be a prelude of the team's FA Cup fifth-round tie at the same stadium in mid-February.
Former leaders Arsenal, who dropped two points in 2-2 draw at Southampton on Tuesday and are now one behind City, face improving Crystal Palace at home on Sunday in a rarely-played derby between the two London sides.
Arsenal have lost three times against Palace in 34 matches since they first met 80 years ago and while they should beat them again as they usually do, Palace have become far more resilient since Tony Pulis became manager in November.
Palace were bottom when Pulis arrived but are now 14th, five points clear of the relegation zone after losing only one of their last four league games.
Palace striker Marouane Chamakh would like nothing more to score against the side that let him leave last year, but Arsenal have only conceded three goals in their current unbeaten nine-game run.
The Gunners will be without Mathieu Flamini, starting a four-match ban after being sent off against the Saints, but it would still be a major surprise if they did not take all three points.
Liverpool strengthened their claims for a top-four finish for the first time since 2009 when they crushed Everton 4-0 in the Merseyside derby on Tuesday and look capable of extending their unbeaten six-match run when they travel to 15th-placed West Bromwich Albion on Sunday.
England international Daniel Sturridge has returned after injury with five goals in four matches including two against Everton, while Luis Suarez, who scored a hat-trick against West Brom in a 4-1 win at Anfield in October, will be looking to inflict more damage and add to his 23 league goals.
Everton, who have slipped from fourth to sixth in the last two weeks, will be looking for a quick return to form against erratic Aston Villa, but will have to look elsewhere for goals following top scorer Romelu Lukaku's ankle injury against Liverpool which could sideline him for weeks.
Tottenham, smarting from Wednesday's crushing defeat, visit Hull City for the third meeting between the teams this season following Spurs' 1-0 victory in the League and their 8-7 penalty shootout win in the Capital One Cup after a 2-2 draw at White Hart Lane.
Hull, who lost 1-0 at Palace on Tuesday, have never beaten Spurs at their KC Stadium, and will be looking to end a streak of four successive Premier League defeats, their worst run of the season.
Manchester United, boosted by the arrival of 37.1 million pound ($61.5 million) club record signing Juan Mata who had a fine debut in the 2-0 win over basement club Cardiff City on Tuesday, face another old favourite on Saturday.
They make the short trip to Stoke City, managed by ex-United striker Mark Hughes, for the second time in five weeks after winning a Capital One Cup quarter-final there 2-0 last month.
Stoke badly need a win after no victories in eight league matches, a run which has seen them slip from 10th to 16th in the last month, while seventh-placed United need to close the gap on the top four.
The weekend kicks off with the always fiercely passionate north-east derby between Newcastle United and Sunderland, who are looking to complete a league double over Newcastle for the first time since 1966-67.
Sunderland's results have steadily improved since Gus Poyet became manager in October culminating in their Capital One semi-final success over Manchester United last week which has set them up for a Wembley date with Manchester City in March.
In the weekend's other matches, Cardiff City host Norwich City, struggling Fulham entertain Southampton and West Ham are at home to Swansea.