Only Kevin De Bruyne, Sergio Aguero and Danilo remain from the side that began against the Terriers, with a number of first team stars rested.
Benjamin Mendy is named a substitute after several weeks out.
The Blues include several Academy graduates in the 18-man squad and Ian Carlo Poveda makes his first senior appearance.
Philippe Sandler makes his first start after one appearance from the bench.
Luke Bolton, Felix Nmecha and Taylor Richards could all be handed debuts from the subs' bench, too.
Pep Guardiola may also look to blood one or two of the youngsters during the course of the game.
Starting XI and bench
As we’ve seen throughout the campaign, the Blues have a system that works extremely well and no matter what the personnel or the age group, the style and thinking is still the same.
So, we should expect the same slick passing game, press and 4-3-3 formation.
More minutes for senior stars
Danilo’s form means he keeps his place at right-back, though has missed much of the campaign with injury.