Carlo Ancelotti says James Rodriguez has "recovered well" and has a chance of featuring as Everton aim to extend their unbeaten run to nine matches.
The Colombian suffered a knock in last weekend's 2-2 Merseyside derby draw at Goodison Park and looked set to miss the game at St Mary's Stadium. Ancelotti, however, revealed James was "partially involved" in Everton training on Friday and his fitness will be assessed ahead of Sunday's contest.
Club Captain Seamus Coleman (hamstring) will miss the game, while Jonjoe Kenny remains sidelined with an ankle problem.
Mason Holgate is unavailable with a toe injury, while fellow centre-back Jarrad Branthwaite is training individually as he recovers from an ankle problem. Striker Cenk Tosun (ACL) and midfielder Jean-Philippe Gbamin (Achilles) are both continuing their rehabilitation programmes.
Richarlison misses out through suspension.
Southampton will be without forward Moussa Djenepo (hamstring), while on-loan winger Theo Walcott is not eligible to play against his parent club.
Stuart Armstrong is in contention to play having completed a period of self-isolation after testing positive for COVID-19.
HOW CAN I WATCH THE GAME?
Sunday's match is being screened live on Sky Sports. For those who do not have a Sky Sports subscription, free live radio commentary is available for digital members on the evertonfc.com Match Centre, with former Everton favourite Sylvain Distin providing expert analysis. The Match Centre also features our live blog, which includes video, imagery and in-game stats. Click here to become a digital member for free.
2020/21 STATISTICS (PREMIER LEAGUE)
Dominic Calvert-Lewin: 7
James Rodriguez: 3
Lucas Digne: 433
Danny Ings: 4
Che Adams: 2
Kyle Walker-Peters: 408
Oriol Romeu: 16
ONE TO WATCH: Nathan Redmond
Skilful and direct forward Nathan Redmond provides a key attacking outlet for Southampton.
An intelligent and versatile footballer, Redmond usually operates from the left flank but is also comfortable on the opposite wing or playing as a second striker.
He has had a direct involvement in 40 Saints goals since joining the south coast club from Norwich City in 2016, scoring 23 times and providing 17 assists.
Redmond, 26, has one senior England cap to his name, having made his international debut in a 1-0 defeat to Germany in March 2017.
REFEREE: Kevin Friend
VAR: Simon Hooper