Manchester derby, Champions League, Chelsea - Matches Man City star De Bruyne is set to miss
The Belgium midfielder only recently returned to first-team action from damaging the lateral collateral ligament in his right knee in August.
During the closing stages of City's 2-0 EFL Cup win over Fulham on Thursday, De Bruyne suffered damage to his left knee in a challenge with Timothy Fosu-Mensah and must now return to the sidelines for five to six weeks
Pep Guardiola's side have coped impressively without their talisman so far this term, going unbeaten over the course of the first 10 Premier League games to sit above Liverpool at the summit on goal difference.
They also lead the way in their Champions League group, but will they be able to maintain their form without the expected boost of a fully fit De Bruyne during a busy period? Here are the games the 27-year-old is likely to miss.
PEP: @DeBruyneKev is out and we are sad for him, nobody likes to have injured players but he will come back to the player he is and he will be fine. It is what it is but fortunately it is not surgery and he will be back. #mancity
— Manchester City (@ManCity) November 2, 2018
November 4 - Southampton (H)
City needed injury-time winners to see off Southampton in both their Premier League meetings last season, with De Bruyne's raking pass setting up Gabriel Jesus to snatch a 1-0 victory at St Mary's on the final day of the campaign. Saints' struggles for goals and form under Mark Hughes this time around suggest this should be a less fraught encounter, even allowing for De Bruyne's woes.
November 7 - Shakhtar Donetsk (H)
City can tighten their grip on Group F by seeing off Shakhtar, who they impressively swatted aside 3-0 in the reverse fixture last week. That was De Bruyne's first start of the season and he scored a stunning opening goal in Manchester when the sides met in the round-robin phase last year, setting up a 2-0 triumph.
November 11 - Manchester United (H)
De Bruyne was rested on the bench for City's home derby back in April and was unable to arrest United's stunning 3-2 turnaround after being introduced in the 72nd minute. Since moving to the Etihad Stadium, he has repeatedly proved himself to be a man for the big occasion and will be sorely missed by Guardiola here.
Three years of @DeBruyneKev... #onthisday, we signed King Kev! pic.twitter.com/bDNhUzsxUJ
— Manchester City (@ManCity) 30 August 2018
November 24 - West Ham (A)
Belgium's Nations League double-header against Iceland and Switzerland is now also off the agenda for De Bruyne and City's next game after the international break comes against West Ham and Manuel Pellegrini, the man who made him the club's record signing – at the time – when he joined from Wolfsburg in August 2015.
November 27 - Lyon (A)
City's only defeat this season came courtesy of a limp 2-1 reverse in the Champions League at home to Bruno Genesio's men. If they can gain revenge in France, it should wrap up progress to the knockout stages.
December 1 - Bournemouth (H)
If De Bruyne makes another ahead-of-schedule return, it will bring Bournemouth into view. Eddie Howe has seen the City star excel with two goals and as many assists in six wins out of six against the Cherries, so will hope he exercises caution.
December 4 - Watford (A)
Like Bournemouth, Watford have had no joy against City with De Bruyne in their line-up. His record against the Hornets reads played five, won five and the two encounters at Vicarage Road under Guardiola have finished 5-0 and 6-0.
What's it like playing alongside @DeBruyneKev? pic.twitter.com/Wfiddz1vXZ
— Manchester City (@ManCity) 10 February 2018
December 8 - Chelsea (A)
A game likely to stand as the main target during De Bruyne's rehabilitation. City eased to a 2-0 win over Chelsea in the Community Shield but Maurizio Sarri's men have not tasted defeat since, firmly establishing themselves as title rivals. In the corresponding fixture last season, De Bruyne scored the only goal to secure a landmark win in Guardiola's quest for Premier League glory.
December 12 - Hoffenheim (H)
City conclude their Champions League campaign against Julian Nagelsmann's side. David Silva hit a late winner when the sides met in Germany last month, while De Bruyne netted three in six versus Hoffenheim during his spells in the Bundesliga with Werder Bremen and Wolfsburg.