Pep Guardila's side are still competing in both the FA Cup and the Champions League - which restarts in August - but their win last time out showed they still have a point to prove.
Southampton arrive in good form having won two from three following the restart. They've now reached the all-important 40 points, but a win would all-but guarantee safety for Ralph Hasenhuttl's men.
Date, time and venue
Southampton vs Manchester City is scheduled for a 7pm BST kick-off today.
The match will be behind closed doors at St Mary's Stadium with no fans due to be present due to government guidelines regarding coronavirus.
How to watch
TV channel: Southampton vs Manchester City is one of four games that will be shown on BBC One following the Premier League's restart, with programming starting from 6:35pm BST.
Live stream: The match will also be streamed on BBC iPlayer and the BBC Sport website, with radio coverage on BBC Radio 5 Live.
Southampton's Sofiane Boufal is expected to miss a third straight game due to the thigh injury he suffered in training.
Pierre-Emile Hojbjerg - who was recently replaced as captain by James Ward-Prowse - is also a doubt after sustaining an ankle injury against Arsenal.
Jack Stephens and Moussa Djenepo can both return after serving suspensions, but Jannik Vestergaard is struggling with injury.
Sergio Aguero remains Manchester City's only injury concern, though they will also be without Leroy Sane - who has now completed a big-money move to Bayern Munich.
Pep Guardiola will most likely rotate his team from the one that dismantled Liverpool, however. The likes of Bernardo Silva, David Silva and Riyad Mahrez could all come back into the team.
Fernandinho can also return to Guardiola's side after completing a one-match suspension
Prediction: Southampton 1-3 Manchester City
With Danny Ings in the side, Southampton always have a chance of scoring. But City were simply sublime against Liverpool and it's difficult to see anything but another win.
City do have to keep an eye on both the FA Cup and Augusts' Champions League return, but with Phil Foden flying, I expect they'll be too much.
Head to head (h2h) history and results
City have won 36 of 92 games between the two teams, including a 2-1 victory in the reverse fixture earlier this season.
Southampton, on the other hand, have won 31, with 25 draws.
Betting odds and tips
- Southampton to win: 17/2
- Manchester City to win: 3/10
- Draw: 5/1
Odds courtesy of Betfair Exchange. Click here to find out more.
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