The Citizens followed up their last-gasp 2-1 win at Wolverhampton Wanderers last weekend with a thumping 5-0 victory at home to Sparta Prague in the Champions League on Wednesday night.
Pep Guardiola's men will now shift their focus back to the Premier League and can climb to the top of the table with victory over Southampton, before current leaders Liverpool face third-placed Arsenal on Sunday.
Here, Sports Mole rounds up Man City's latest injury and suspension news ahead of the contest with Russell Martin's side.
Rodri
Status: Out
Type of injury: Knee
Possible return date: Unknown
Man City will be without influential midfielder Rodri for the rest of the season after he suffered knee ligament damage in a 2-2 draw with Arsenal last month.
Oscar Bobb
Status: Out
Type of injury: Leg fracture
Possible return date: Unknown
Oscar Bobb sustained a fracture to a bone in his leg during a training session in August and was initially ruled out for between three and four months, but Guardiola has since revealed that the attacker is targeting a return between January and February of next year.
Kevin De Bruyne
Status: Out
Type of injury: Groin
Possible return date: Unknown
Kevin De Bruyne has missed Man City's last seven matches with a groin injury and although he has returned to training, Guardiola has revealed that the playmaker "doesn't feel good" and will only make his comeback when he is 100% fit.
Kyle Walker
Status: Out
Type of injury: Knee
Possible return date: Unknown
Kyle Walker has missed Man City's last two games after picking up a knee injury on international duty with England. Guardiola has since confirmed that the right-back has 'not been well' and is unable to put a timeframe on his return.
Jack Grealish
Status: Out
Type of injury: Knock
Possible return date: November 2 (vs. Bournemouth)
Jack Grealish missed Man City's win over Sparta Prague and Guardiola revealed prior to the match that the Englishman is set to be out for between seven and 10 days with an unspecified knock.
Jeremy Doku
Status: Out
Type of injury: Muscle
Possible return date: November 9 (vs. Brighton)
Jeremy Doku also missed Man City's win over Sparta Prague and Guardiola revealed prior to the match that the winger will be out for "a little longer" than Grealish, meaning the Belgian is facing at least a couple of weeks on the sidelines.
MANCHESTER CITY'S SUSPENSION LIST
Manchester City have no suspended players for this match.