After being unavailable for selection against Wolves last weekend, Yerry Mina, Kurt Zouma, Bernard and Andre Gomes are all in the running to feature.
With that in mind, here is how Everton are likely to line up against the Saints.
1. Goalkeeper & Defenders
Jordan Pickford (GK) – The England number one impressed everyone at the World Cup and returned to Premier League duty last week against Wolves. He will start again here.
Seamus Coleman (RB) – Always an option on the right hand side, Coleman’s partnership with Theo Walcott has proved to be a good combination in attack.
Yerry Mina (CB) – After Phil Jagielka’s red card against Wolves, it is expected either Kurt Zouma or Yerry Mina will feature for Everton against the Saints. Mina is the option that Silva will most likely go for as the captain’s replacement.
Michael Keane (CB) – Despite some shaky moments in the opening fixture of the season, Keane is likely to keep his starting position. His partner in defence is up for debate but Keane will need to perform well as it may already be a make or break season for the Englishman.
Leighton Baines (LB) – A solid performance against Wolves, with a delightful cross that led to the opening goal of the game, proves that the 33-year-old still has something to give for the team.
Theo Walcott (RM) – A solid performance against Wolves and a good partnership forming with Coleman means the 29-year-old is bound to start on Saturday.
Idrissa Gueye (CM) – The combative midfielder has struck up a good partnership with Morgan Schneiderlin and it worked well against Wolves.
Morgan Schneiderlin (CM) – After struggling at the beginning of his Everton career, Schneiderelin has since impressed, none more so than his solid performance against Wolves.
Richarlison (LM) – A dream debut for the 21-year-old Brazilian against Wolves was cut short with a slight muscle injury. The injury is not thought to be serious, so the talented winger is bound to keep his starting spot for Everton.
Gylfi Sigurdsson (AM) – Sacrificed in the Wolves game after the red card to Jagielka, Gylfi Sigurdsson will no doubt regain his starting spot against Southampton. The Icelandic playmaker was instrumental in games last season, and the invention he has in his locker will be used to the maximum against the Saints.
Cenk Tosun (ST) – Started the game against Wolves, connected the attacking play very well, assisting Richarison’s second goal, and caused the defence problems. Oumar Niasse also played well when he replaced Tosun in the latter stages of the game, but Tosun seems to be the favoured striker this season.