Unbeaten Liverpool are clinging on in the title race - scoring deep into added time against Everton last week and recovering from a goal down to beat Burnley on Wednesday to move just two points behind City.
Elsewhere, all eyes will again be on the next instalment in the Old Trafford soap opera, with stuttering Manchester United hosting bottom club Fulham.
Tottenham - yet to register a single draw in the Premier League this season -- are away to Leicester. Arsenal play lowly Huddersfield.
AFP Sports picks out some of the main talking points ahead of the weekend fixtures in the Premier League.
Chelsea seek to arrest slide
Chelsea were unbeaten in their first 12 Premier League games, determinedly hanging on to the coat-tails of Manchester City and Liverpool.
But if they lose to Pep Guardiola's league leaders at Stamford Bridge on Saturday they will be looking at a yawning gap of 13 points -- and it would be their third defeat in four league games.
Chelsea defender Marcos Alonso has urged his teammates to forget about the gap, which already looks ominously big.
"If we lose we are going to be 13 points from the top and that's a lot of points but we have to think, prepare for the game well and not pay attention to the table at the moment," he said. "It's the perfect opportunity to come back."
Does Mourinho know his best team?
Jose Mourinho is desperately casting around for solutions to the malaise at Old Trafford -- but is all the chopping and changing hindering, rather than helping?
Manchester United have made a total of 46 changes to their starting XI in the Premier League so far this season, including seven changes on Wednesday against Arsenal -- more than any other team in the competition
Former United defender Rio Ferdinand is concerned over the tinkering.
"Something needs to be done," Ferdinand said in his role as a pundit for BT Sport. "The common thing that we've seen with this team under Mourinho is changes every week -- changes, changes, changes.
"That doesn't bode well for me in terms of the players and for the team because you need to form relationships within a team and you can't do that when there's chopping and changing, week in and week out."
Will Klopp ring changes again?
Jurgen Klopp made seven changes for his side's midweek match against Burnley -- starting without any of the front three of Sadio Mane, Mohamed Salah and Roberto Firmino for the first time since September 2017.
Despite a scare at Turf Moor, Liverpool won 3-1, taking their tally to 39 points after 15 matches -- more than any other Anfield side in history.
On Tuesday they face Napoli at Anfield with the prospect of crashing out of the Champions League group stage just over six months after reaching the final -- but first they must negotiate a trip to high-flying Bournemouth.
Arsenal: a team of two halves
For a side that is unbeaten in 20 matches, Arsenal have the curious record of not once leading at half-time in a Premier League game this season.
Wednesday was no different, as Manchester United pegged them back to reach half-time at 1-1.
But Arsenal have scored more second-half goals than any other team -- 25 -- and four points in their past two games against Spurs and United suggest Unai Emery is adding steel to a side that had flatlined under Arsene Wenger.