Pep Guardiola, who has signed a two-year contract extension at the club, has been working with a squad down to its bare bones for some time and oversaw a run of four successive defeats in all competitions prior to the international break for the first time in his managerial career.
The Citizens have been boosted by the return to training of as many as seven players over the last week or so, and Guardiola has confirmed that some of those - potentially all of them - could be involved in Saturday's Premier League clash against Tottenham Hotspur at the Etihad Stadium.
However, five players are in the treatment room including long-term absentees Rodri and Oscar Bobb who continue to recover from respective ACL and leg injuries.
Ruben Dias (calf) and youngster Max Alleyne (unspecified) are also sidelined, while Guardiola has confirmed that Mateo Kovacic is the latest name to pick up an injury.
How long will Kovacic be out for and what games could he miss?
Speaking at a press conference on Friday, Guardiola confirmed that Kovacic will be out for "a while", adding that he is set to miss "three weeks or a month, more or less" with his unspecified problem.
Kovacic, who has played 15 times in all competitions for Man City this season, was hurt while playing for Croatia in a 1-1 draw with Portugal in the UEFA Nations League on Monday, and was substituted at half time.
It remains unknown as to whether Kovacic has sustained a muscle injury or more of a knock, but if it is the former, then Man City's medical staff will likely take a precautionary approach with the midfielder's recovery.
Kovacic will definitely miss Saturday's Premier League clash with Spurs, while he is also set to miss Man City's next five games across all competitions over the next three weeks.
A Champions League encounter at home to Feyenoord will take place next Tuesday, while Man City will also have to cope without Kovacic for a top-of-the-table Premier League showdown against Liverpool at Anfield on December 1.
Back-to-back top-flight fixtures with Nottingham Forest (December 4) and Crystal Palace (December 7) will follow for Man City, before they face Juventus in the Champions League on December 11.
Depending on the severity of Kovacic's injury, the Croatian could target a return for the Manchester derby against rivals Manchester United on December 15, or an away trip to Aston Villa six days later.
Who could replace Kovacic in Man City's midfield?
Kovacic was tasked with filling the void left by Rodri and has been deployed as a deep-lying playmaker in the vast majority of his 15 appearances for Man City across all competitions this season.
Guardiola now has no natural defensive midfielder in his senior squad, but one name who could step up in the absence of Rodri and Kovacic is academy starlet Nico O'Reilly, who is yet to make his Premier League debut but has played centrally on four occasions in other competitions this term (once in the Champions League, once in the Community Shield and twice in the EFL Cup).
The Catalan coach could also turn to either Kevin De Bruyne, Bernardo Silva, Ilkay Gundogan or Matheus Nunes to play in a deeper midfield role, and may decide to use two of those rather than just a sole pivot.
Another option Guardiola could explore is using Rico Lewis in a fixed midfield position rather than the teenager drifting into central positions from either right-back or left-back.
Ball-playing defenders John Stones and Manuel Akanji both have experience of stepping out of defence and into a defensive midfield role during matches when Man City are in possession, and they could also be considered for a temporary spell in the middle of the pitch in Kovacic's absence.