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The Blues looked imperious a week ago but lost 1-0 at home to City last weekend and were then beaten by the same scoreline in Turin in the Champions League in midweek.
Those results have left Thomas Tuchel facing some tough questions and he will be hoping Chelsea can respond against Southampton.
The Saints have endured a difficult start to the season and remain winless after four games, though they did hold Manchester City to a 0-0 draw at the Etihad two weeks ago.
Date, kick-off time and venue
Chelsea vs Southampton is scheduled for an 3pm BST kick-off at Stamford Bridge on Saturday.
Where to watch Chelsea vs Southampton
Saturday’s match will not be broadcast live on TV in the UK.
Chelsea vs Southampton lineups and team news
Chelsea XI: Mendy, Chalobah, Silva, Rudiger, Azpilicueta, Chilwell, Loftus-Cheek, Kovacic, Hudson-Odoi, Werner, Lukaku
Subs: Kepa, Alonso, Christensen, Barkley, Jorginho, Saul, Havertz, Mount, Ziyech
Southampton XI: McCarthy, Livramento, Bednarek, Salisu, Walker-Peters, Walcott, Romeu, Ward-Prowse, Tella, Redmond, A. Armstrong.
Subs: Lyanco, Long, Adams, Perraud, S. Armstrong, Djenepo, Elyounoussi, Diallo, Forster.
Chelsea vs Southampton prediction
After a difficult week, Chelsea need to bounce back. They should have too much for Southampton.
Chelsea 3-0 Southampton
Premier League head to head (h2h) history and results
Chelsea wins: 24
City wins: 9
Last meeting: Southampton 1-1 Chelsea (20/02/2021)
Betting odds and tips
Chelsea to win: 1/3
Southampton to win: 8/1
Odds via Betfair (subject to change). Click here to find out more.