The good news for Pep Guardiola's side is the return of midfielder Fernandinho after injury, and the Brazilian is available just in time for what promises to be a hectic three weeks.
Kevin de Bruyne and John Stones could also return at just the right time for City.
Fulham should provide easy fodder for the visitors as they are in freefall back to the English Championship after just one season in the top flight.
League leaders Liverpool have a teatime kick-off at home to third-placed Tottenham Hotspur, whose poor run of form before the international break ended their faint title hopes and has left them looking over their shoulders at Arsenal, who are now just one point behind.
A win for Liverpool would ensure they remain top, but a defeat for Spurs could see them suddenly in real danger of failing to qualify for next season's Champions League, just days before they are due to play their long-awaited first league game in their new stadium.
Saturday is an important day for bottom side Huddersfield, who could become the first team to be relegated this season if they lose away to Crystal Palace and results elsewhere go against them.
The Terriers have just 14 points this season after a terrible sophomore year in the top flight, and their visit to Selhurst Park is one Palace will look to use to put their own relegation fears to bed.
Ole Gunnar Solskjaer will look to celebrate Thursday's news of his confirmation as full-time Manchester United manager with a home win against Watford. Victory for United would pile the pressure on Tottenham ahead of their trip to Anfield.
Survival is on the agenda in the south coast derby between Brighton and Southampton, with just three points separating two teams who currently sit 15th and 16th in the table.
Meanwhile, Leicester City aim to continue their positive run of form and performances since Brendan Rodgers took over from Claude Puel.
Bournemouth, whose away form is far from impressive, beat Leicester 4-2 earlier in the season and will look to take advantage of Harry Maguire's absence from the Leicester defense owing to suspension.
Everton have a tough visit to West Ham United, while Chelsea will have to show more personality than they have at times in recent weeks when they visit Cardiff on Sunday.
Chelsea's defense can expect an aerial bombardment and if the Blues are to get three points from a side fighting relegation, they will need their players to show the commitment that coach Maurizio Sarri has questioned in recent months.