The runaway Premier League leaders have been tested over the past week with a narrow win against Feyenoord in the Champions League and a dramatic late victory against Huddersfield on Sunday.
Crucially, however, they proved their steal as their remarkable 18-game winning run continues.
But those games will have taken their toll - so will Guardiola shuffle the pack against the Saints?
Stuart Brennan
Doubt remains over whether Vincent Kompany can start three games in eight days, and there comes a point when Eliaquim Mangala has to be trusted.
A clash with Southampton is NOT that time however, and personally - and without access to Kompany's physio readings - I would ask him to patch up and go out again.
Mangala would be better suited to the visit of West Ham on Sunday.
But the team does need freshening up, and maybe a run for Gabriel Jesus, who made a difference at Huddersfield, would effect that. Other than that, there is no call for changes, especially with the struggling Hammers and a dead rubber at Shakhtar coming up.
James Robson
It feels like the right time to freshen things up with so many games coming in quick succession.
Guardiola has a big enough squad to make changes without dramatically damaging the quality of his team.
Bernardo Silva has waited patiently, while Ilkay Gundogan has had to make do with only a clutch of opportunities.
Kompany needs to show he can play more than two games a week but this is an opportunity for a few players to come in. Gundogan has impressed whenever he has appeared this season and can give De Bruyne a rest, who seemed to feature unnecessarily against Feyenoord.
Gabriel Jesus can come in too, although it may be best to hold Bernardo for starts against West Ham and Shakhtar.
XI: Ederson, Walker, Kompany, Otamendi, Delph, Fernandinho, Gundogan, Silva, Sterling, Sane, Jesus
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