The Citizens have been victorious in their last 19 matches in all competitions and will enter this contest off the back of a 2-0 win over Borussia Monchengladbach in the Champions League on Wednesday.
Here, Sports Mole looks at how the title hopefuls could line up against the Hammers.
Out: Nathan Ake (muscle)
City will again be without the services of Nathan Ake on Saturday due to a muscular problem, but the league leaders are otherwise in excellent shape for the clash at the Etihad Stadium.
Guardiola is expected to shuffle his pack from the Champions League clash on Wednesday, with John Stones and Oleksandr Zinchenko both in line to return to the back four alongside Joao Cancelo and Ruben Dias.
Gabriel Jesus and Sergio Aguero are both fit and available for selection, but Raheem Sterling could operate through the middle against the Hammers, with Phil Foden and Mahrez operating in the wide areas.
Fernandinho is an option for change in the middle of the park, but Rodri and Ilkay Gundogan are likely to keep their positions, with Guardiola expected to resist the temptation to break up the midfield duo.
Bernardo Silva has been excellent for City in recent weeks but could be rotated out of the side here.
Watch the Sports Mole Football Shorts prediction for this game below: