Of course, the Citizens squad is better placed than most to deal with injuries, but the Frenchman had been one of their most impressive performers this season. He has been reborn under the guidance of Manuel Pellegrini.
The Chilean may even look to alter his setup and formation as his team enter crucial games in four different competitions over the next few weeks, but who are the players he'll be relying upon?
Different members of his squad might be required to play in varying positions in the team as the matches stack up over the next few weeks.
Here are six players whose roles at City could be about to become more important.
The Spaniard has sparkled in parts of his first season in English football but consistency will be key for him now.
The rotation system, which usually saw Navas interchange with Nasri and David Silva in the two most advanced of Pellegrini's midfield positions, will have to be abandoned in the next few weeks. Navas will likely be asked to play in a lot of important matches for his club.
You can almost guarantee that Silva will step up to the plate and perform, but will Navas?
Recent goals against Tottenham, Fulham and Cardiff have showcased his ability to find the net and that quality could be huge for City in Nasri's absence.
Perhaps Navas could learn from Milner's consistency?
The Englishman rarely lets City down whenever he is called upon, and that is now likely to happen a lot more following the injury that Nasri suffered in the recent win at Newcastle.
He might not be the flashiest or the most exciting of players, but Milner could be a crucial influence in the big matches that lie ahead for City.
His terrific performance and goal in the Champions League win at Bayern Munich showcased the fact that he can be relied upon to produce on the big stage and it would be no surprise if Pellegrini selected him for the clashes with Barcelona that lie ahead.
Seemingly one of the forgotten men of English football, Rodwell has three caps for his country yet is now a million miles off a place in the England World Cup squad.
Injuries have decimated the former Everton man's time at the Etihad Stadium, but although he plays in a different position to Nasri, he could now benefit from the Frenchman's absence if Pellegrini opts to switch things around.
Fernandinho, Yaya Toure and Javi Garcia will still be Rodwell's key contenders for a place in the team, but the Englishman can also play as the most advanced of a midfield trio or even on the right side of a 4-4-2.
We may never truly see what he can achieve in a City shirt, with a move away surely what is best for his career, but he could be seen in the team a little more often than usual in the second half of this campaign.
Strictly one for the domestic cup competitions, perhaps we'll now see Marcos Lopes further enhance his City career with a few more appearances in the absence of Nasri.
He is almost certain to figure in the second leg of the Capital One Cup semi-final against West Ham tonight, whilst the forthcoming FA Cup meeting with Watford will also hold good memories for the 18-year-old Portuguese youth international.
Last year, when he'd just turned 17, Lopes scored within seconds of coming on for his City debut in an FA Cup tie against the Hornets. After featuring against Wigan and West Ham in the Capital One Cup this season, he might also be eyeing a spot in the squad for the final, too.
Welshman Emyr Huws, 20, made his City debut in the FA Cup third-round replay against Blackburn Rovers last weekend. He is another player who could see his City appearance record dramatically improve in the next week.
Formerly on loan at Northampton Town and captain of the under-21 side, Huws could figure in the forthcoming matches against West Ham and Watford as he bids to make his mark at City.
The midfielder has been capped six times by his country's under-21 side, and he has already been earmarked by Wales under-21 manager Geraint Williams as a potential future star, per BBC Sport.
Jovetic is another who could benefit from Nasri's absence should Pellegrini seek to alter his attacking line-up.
Although Edin Dzeko and Alvaro Negredo have been in fine form recently, now that Sergio Aguero is back and fully fit, the Argentine has to be considered the side's first-choice forward.
The prospect of Aguero playing at the top of the formation with a finally fully fit and firing Jovetic just off him as the No. 10, perhaps with Silva and Navas on either side, is quite a lineup. For that to happen, the Montenegrin will need to overcome his frequent problems and earn a spot in the side.