Chelsea will be without defender Trevor Chalobah due to the injury that forced him off against Aston Villa on Saturday.
Head coach Enzo Maresca has confirmed that goalkeeper Filip Jorgensen will start despite his costly mistake at the weekend, while Pedro Neto is likely to continue as a centre forward.
Southampton's Jan Bednarek is expected to overcome the knock he sustained at Brighton and fellow defender Taylor Harwood-Bellis could return after missing the last three matches with an ankle issue.
On-loan midfielder Lesley Ugochukwu is ineligible to face his parent club.
Match facts
Head-to-head
Chelsea's two defeats in the past three league meetings is as many as they had suffered in their previous 18 encounters versus Southampton.