Why? The two months Kompany was out of the side through injury at the start of 2013 saw the gap from Man United in first place to City in second go from four points to 15. United were almost out of sight, and Kompany's absence was a significant factor in the Sky Blues' faltering attempt to hang on to their title.
The man himself was hoping to be back after the current international break, but according to Jamie Jackson of the Guardian, it now looks like he'll be out until early October.
With a Manchester derby and the start of the Champions League group campaign falling during his possible absence, it's a blow, which ever way you slice it.
So, how do City adjust to life without their skipper?
Kompany 's successful partnerships with both Joleon Lescott and more recently Matija Nastasic will have been built on an understanding developed over time, and good communication. Whichever defensive combination Manuel Pellegrini selects will not have had the luxury of time to develop, so good communication will be essential.
City's poor performance in losing to Cardiff and the odd wobble in the win over Hull showed signs of a defence still gelling. In south Wales, Javi Garcia, a midfielder by trade, was shunted back to partner Lescott with Nastasic still unavailable with a knee injury; the results weren't great.
Nastasic returned for Hull, but City were lucky when Sone Aluko shot wide early on after carving through the middle like a hot knife through butter. The Serbian is likely to be paired with Lescott again when City face Stoke, and the duo will have to up the ante when it comes to communicating with each other.
Kompany has also developed a good understanding with Joe Hart over the years, and even though the pair have been seen to bicker at times, that's a sign of strong personalities battling for the common good. The central-defensive partnership will have to keep an open channel with their goalkeeper over the coming fixtures.
How else does Pellegrini explore his options without Kompany? Without wanting to denigrate the competition, the Capital One Cup may be the place to experiment in the back four.
It has been a while since Micah Richards plied his trade in central defence, but with Martin Demichelis also injured, the tie against Wigan on September 24 may be a good time to try the England international in the middle rather than at right-back. This would give someone a break, just two days after the derby, and give Richards some much-needed game time that he may not get before then.
Whatever Pellegrini decides to do should Kompany definitely miss this crucial phase of the season, the players he puts out must step up and embrace a challenging few weeks.
Kompany would relish these forthcoming encounters by throwing himself into them wholeheartedley, and his team-mates must do so too if they are to come through a potentially season-defining period unscathed.