Unbeaten City set the pace after six games with 16 points. They have scored 21 goals and conceded twice. They lost both Premier League games against Chelsea during the last campaign.
And their defensive resources suffered a serious blow when full-back Benjamin Mendy was ruled out for at least six months after undergoing an operation on a ruptured anterior cruciate ligament.
Mendy, 23, had been in fine form for City since his 57 million euro move from the French champions Monaco.
City will also be without six goal striker Sergio Aguero for up to a month. The 29-year-old Argentina international was injured in a car crash on his way back from a concert in Amsterdam on Thursday.
"It's a broken rib. Hurts, but I'm fine, fully focused on recovery," tweeted Aguero after checks by City medical staff on Friday.
Both City and Chelsea, who are three points behind both Pep Guardiola's men and second placed Manchester United, go into Saturday's game on the back of midweek Champions League victories over Shakhtar Donetsk and Atletico Madrid respectively.
City beat the Ukrainians 2-0 at the Etihad while Chelsea needed a stoppage time winner from Michy Batshuayi to overcome Atletico 2-1 in their lavish new stadium Wanda Metropolitano.
Chelsea manager Antonio Conte is unhappy that, while City played at home on Tuesday, his side have had a short turnaround after arriving back in London on Thursday morning. "I think we are a bit penalised," said Conte. "Man City is a really strong team. They are scoring a lot of goals and they are in a good moment of form.”
Conte, who led the Blues to the Premier League title in his first season at Stamford Bridge, added: "There is the international break after this weekend’s games. My surprise is for this because there is the time to play the game later."