City will have a completely fresh midfield against Southampton, with David Siva, Bernardo and Fernandinho all returning.
Both full-backs are changed with Joao Cancelo and Oleks Zinchenko coming in for the not fully fit Kyle Walker and Benjamin Mendy.
Riyad Mahrez also returns.
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Line-ups
City XI: Ederson, Cancelo, Zinchenko, Garcia, Laporte, Fernandinho, D Silva (c), Bernardo, Mahrez, G Jesus, Sterling
Subs: Bravo, Stones Gundogan, Rodrigo, De Bruyne, Otamendi, Foden, Doyle, Harwood-Bellis
Southampton XI: McCarthy, Walker-Peters, Stephens, Bednarek, Bertrand, Armstrong, Ward-Prowse, Romeu, Redmond, Ings, Adams
City aiming to keep momentum going
With four wins from five, 15 goals scored and four clean sheets, City are undoubtedly the form team of the post-lockdown Premier League and FA Cup.
Pep Guardiola admits he wants his team in tip-top condition for the FA Cup semi-final with Arsenal and the Champions League clash with Real Madrid, so there can be no let-up in the six league games that remain.
Southampton represent an interesting hurdle and in Danny Ings, they have a striker at the top of his game.
If City can keep Ings quiet, there will be a chance to inflict an 11th home loss on the Saints this season - and that would be an unwanted club record for the hosts.
Stats and facts
City’s 4-0 victory against Liverpool was their 25th Premier League win by at least four goals under Pep Guardiola - seven more than any other club in that time.
City will look to avoid losing three consecutive away league games for the first time since April 2015.
Pep Guardiola has never lost three consecutive away league matches in his managerial career.
Saints could lose seven successive Premier League matches against Manchester City for the first time
Kevin De Bruyne has been directly involved in more Premier League goals than any other player this season, scoring 11 and assisting 17.
De Bruyne has created more chances (432) and set up more goals (62) than any other player since his City debut in 2015.
He has registered 17 Premier League assists this season, just one shy of his best tally of 18 in 2016-17.
Phil Foden has scored six goals and provided eight assists in his last 17 appearances in all competitions, despite making only 10 starts.
City have won 10 of the past 12 Premier League meetings, including the last six by an aggregate score of 17-4.
Southampton could register an 11th home defeat of a single campaign for the first time in all 92 seasons of their league history.
Saints have conceded 33 goals at home this season.
Southampton have 40 points after 32 matches, already surpassing their total in 2017-18 (36) and 2018-19 (39).
