The Citizens will be expected to respond with a ruthless attacking display against a side which has not won away from home since April.
City's setback in East Anglia was their first defeat in the league since January and, more importantly, revealed some weak spots in this Guardiola side.
In the absence of Aymeric Laporte, who is set to be out for around six months, the defensive partnership of John Stones and Nicolas Otamendi failed to engender the feeling of total control which is normally emblematic of any Guardiola side.
Indeed, the Catalan boss has only used the pair together on 25 occasions since becoming manager in 2016, and effectively abandoned the idea of deploying the duo after City's 4-3 defeat at Anfield in January 2018.
The injury this week to Stones, however, has left Guardiola with just one fit central defender - Otamendi - for the next month at the very least, leaving City short in that department and perhaps vulnerable to further surprise defeats to lesser opponents.
However, the insertion of Fernandinho into central defence - something Guardiola has done before - worked well during City's comfortable 3-0 win over Shakhtar Donetsk in Kharkiv on Wednesday, and with the spellbinding attacking talent at the manager's disposal, City will be expected to outscore virtually every team they come up against - especially at home.
City come up against a potentially dangerous Watford side, whose superb comeback from two goals down at home to Arsenal last weekend was demonstrative of a team enjoying a fresh lease of life under Quique Sanchez Flores, who was reappointed over the international break after the club axed Javi Gracia following a run of three defeats in four games.
Watford's decision to reinstate Flores, who spent the 2015-16 season at Vicarage Road, falls in line with a ruthless policy of continuous evolution which has seen no manager aside from Gracia spend longer than a season at the club since 2013.
Perhaps this method precludes the emergence of a distinct footballing identity like at the Etihad, but the policy has turned the Hornets into a closely-knitted, deeply organised unit whose core group of players includes the likes of Troy Deeney, Will Hughes, Abdoulaye Doucoure, Tom Cleverley, Christian Kabasele and Daryl Janmaat - hardly showbiz names but highly dependable ones.
Guardiola will be mindful of the fact that, since returning to the Premier League in 2015, Watford have beaten Chelsea and Liverpool 4-0 and 3-0 respectively, alongside claiming smash-and-grab wins over Manchester United, Arsenal and Tottenham Hotspur.
On the other hand, Watford supporters will head into this game knowing that City only lost once at home in the league last season and recorded the biggest margin of victory in an FA Cup final since 1903 against their side back in May, cruising to a 6-0 victory at Wembley.
The visiting team will know that it will take the game of their lives, combined with another defensive collapse from City, in order to claim an unlikely three points in Manchester this Saturday.
Manchester City form: WDWWL
Watford form: LLLDD
As already mentioned, Stones is set to miss a month of action after suffering a muscular injury in training ahead of the win over Shakhtar, although Phil Foden is expected to return to the squad having missed the trip to Ukraine due to illness.
The only other injuries for City are the two long-term absentees, Laporte and Leroy Sane, with the former set to miss at least six months and the latter expected to come back in either January or February.
Watford will be without Deeney, their captain and talisman, for around two months after the Englishmen underwent knee surgery at the end of August.
Craig Cathcart is the only other Watford player ruled out for this game after he confirmed to the media earlier this month that he would miss the first pair of league games after the international break due to a thigh injury sustained whilst playing for Northern Ireland.
Manchester City possible starting lineup:
Ederson; Cancelo, Fernandinho, Otamendi, Mendy; Rodri, De Bruyne; B Silva, D Silva, Sterling; Aguero
Watford possible starting lineup:
Foster; Janmaat, Dawson, Kabasele, Femenia; Doucoure, Capoue; Hughes, Cleverley, Deulofeu; Pereyra
We say: Manchester City 4-0 Watford
If Wednesday's dominant performance against Shakhtar was anything to go by, the defending champions have been reinvigorated rather than cowed by that defeat to Norwich, and will be even more determined to put on a show in front of their own fans against a side they have beaten by five goals or more on three separate occasions since May 2017.