Kompany picked up a calf problem while on international duty with Belgium last week.
Both sides will also have to check on the fitness of their returning internationals, and indeed the two clubs shared the cost of a private plane to fly back their Brazilian players in time for the lunchtime showdown.
MAN CITY INJURIES
Kompany picked up a knock while with Belgium, and though Guardiola says it is not a long-term injury, the captain will not be able to face Liverpool. Guardiola would most likely have to pair up John Stones and Nicolas Otamendi in a four-man defence, something which has not always worked out well.
Ilkay Gundogan has stepped up his recovery from a long-term knee injury and could feature in the squad. Guardiola plans to use the German at the base of midfield this season, though a start against a high-pressing Liverpool side would be a tricky reintroduction.
MAN CITY SUSPENSIONS
Raheem Sterling will serve a one-match ban following his controversial red card at Bournemouth, though City will welcome back Kyle Walker from his ban.
MAN CITY POTENTIAL STARTING LINE-UP
Guardiola switched from a 3-4-3 to a 4-3-3 at Bournemouth before the international break, and he could stick with the same shape for the Liverpool game.
Although the 3-4-3 (if used well) would give City more control over the game, it has meant centre-backs Otamendi and Kompany have seen a lot of the ball this season. They have not looked particularly sure-footed in possession, and they could both be pressed into errors by Liverpool's attack.
That said, Guardiola may have no choice but to stick with a four-man defence now that Kompany is ruled out, unless Eliaquim Mangala or Tosin Adarabioyo are selected as part of a back three.
Stones missed out at Bournemouth and should now come back into the team.
Fernandinho has often been the out ball for City's defenders, but the Brazilian can also be forced into trouble. Gundogan, when fit, will be given the role, but it seems he will not be thrown in at the deep end this weekend.
Raheem Sterling is banned for the game, meaning it should be between Sergio Aguero and Leroy Sane for the spare forward role.
Whether in the 4-3-3 or 3-4-3, Gabriel Jesus and one of Aguero or Sterling are slated to play close to one another up front, with one of the attacking midfielders taking up the other role. At Bournemouth, Sterling and Bernardo Silva played off Jesus, and their runs inside allowed the full-backs attacking down the flanks. That suggests Bernardo Silva, who tends to come inside more than Sane, could continue in the team.
LIVERPOOL TEAM NEWS
Philippe Coutinho could be back in the squad for Saturday's game, though it remains to be seen exactly how he will react to having a move to Barcelona blocked.
The Brazilian has not featured at all so far this season, with injury and illness cited as the reasons.
Nataniel Clyne will miss this game and indeed several more months of the season with a back injury, and Adam Lallana is another long-term absentee.
Klopp will have to check on the fitness of his internationals, including Roberto Firmino, Sadio Mane and Mohamed Salah.
Alex Oxlade-Chamberlain could make his debut following his move from Arsenal.
Loris Karius was named in goal for the Reds' final game before the international fixtures, with Simon Mignolet left out of the squad. Though Arsenal rarely threatened Karius' goal, he did twice lose possession in his own area, which could offer City some encouragement.
OPTA MATCH FACTS
- Manchester City have lost only one of their last eight home Premier League meetings against Liverpool (W4 D3), a 1-4 defeat in November 2015 which remains the last time City lost by three goals in a home Premier League game.
- Liverpool have won three of their four Premier League games against Man City since Jurgen Klopp took charge, drawing the other in March last season.
- Under Jurgen Klopp, Liverpool have lost just one of their 22 Premier League matches against a team that finished in the top seven of the competition last season (W12 D9 L1).
- In this period, Liverpool are unbeaten away from home against last season’s top seven sides in the Premier League (P9 W5 D4 L0).
- Sadio Mané has scored seven goals in his last nine Premier League games, including a goal in each of his last four appearances in the competition.
- Gabriel Jesus has been directly involved in 12 goals in his 11 Premier League starts for Man City (eight goals, four assists).
TV COVERAGE & KICK-OFF TIME
Kick off is 12:30 BST with the game to be shown live on Sky Sports Main Event and Sky Sports Premier League, as well as for subscribers on the Sky Sports app.