Premier League defeats by Wolverhampton Wanderers and Arsenal before the international break jolted the serene early-season form of the champions and left them third in the table, two points behind Tottenham Hotspur and Arsenal.
Sixth-placed Brighton, managed by Italian Roberto de Zerbi who is highly rated by Guardiola and who many predict could one day replace him, look capable of adding to City's woes.
The only time Guardiola lost three league games in a row was as Bayern Munich manager in 2015 but for that to happen to his City side would have seemed unthinkable a few weeks ago.
A Brighton win would actually move them above City in the table and if that were to happen, it would hardly be a surprise to those who have watched their progress.
De Zerbi has instilled a brand of football at the South Coast club that has striking resemblances to City's progressive possession-based style, with some even suggesting he has taken the Guardiola blueprint and evolved it.
He took them to sixth place last season and into Europe for the first time and it was clearly no flash in the pan with wins against Newcastle United and Manchester United already in the bag this campaign, as well as a draw this month with Liverpool in what was De Zerbi's 50th game in charge.
De Zerbi spent some time at City's training ground studying Guardiola's methods after leaving Shakhtar Donetsk and before joining Brighton, spending hours in deep discussions about their respective football philosophies.
Before the sides played out a 1-1 draw at Brighton at the end of last season, Guardiola described De Zerbi as "one of the most influential coaches of the last 20 years" and said the way Brighton play was "unique".
High praise indeed, but the mutual admiration society will be put on hold for 90 minutes on Saturday as City attempt to regain top spot, at least until second-placed Arsenal take on Chelsea at Stamford Bridge in a later kickoff.
City will be boosted by the return of key midfielder Rodri after his red-card suspension while striker Erling Haaland will be keen to avoid going three league games without a goal.
Arsenal's home win over City before the international break was a huge psychological boost for the Gunners who caved in under City's pressure in last season's title race.
They will face a stern test at Chelsea, however, even if Mauricio Pochettino's side are languishing in 11th place.
Chelsea's displays have been better than their points haul suggests and back-to-back wins over Fulham and Burnley have established some momentum for the west Londoners.
Surprise leaders Tottenham Hotspur have to wait until Monday to resume their best-ever start to a Premier League season when Ange Postecoglou's side host Fulham.
The weekend action gets underway with the Merseyside derby with fourth-placed Liverpool hosting 16th-placed Everton.
Everton have managed only one win in the last 28 clashes against Liverpool in all competitions but are in reasonable form after two wins in their last three league games.
Manchester United's last game before the international break was a dramatic late escape against Brentford with two Scott McTominay goals in stoppage time earning a 2-1 victory.
Had they lost that game, manager Erik ten Hag would have been under extreme pressure but with an away game against bottom club Sheffield United on Saturday, the Dutchman has the chance to get his 10th-placed team moving in the right direction.
