The Toffees, who are currently seventh in the table, recorded a famous 2-0 win over bitter rivals Liverpool last weekend, while Southampton will enter the contest off the back of a 3-0 defeat at Leeds United.
Goals from Richarlison and Gylfi Sigurdsson handed Everton a long-awaited Premier League win over Liverpool at Anfield last weekend and fuelled suggestions that the Toffees could challenge for a top-four position.
Heading into this weekend's fixtures, Carlo Ancelotti's side are seventh in the table, five points behind fourth-placed West Ham with a game in hand, while they are now level on points with sixth-placed Liverpool, also with a game in hand, and could potentially go above the champions in the table on Monday night.
Everton have actually lost eight of their 24 league games this term, though, which is a high number considering their position in the table, while their recent home form in England's top flight has been disappointing, suffering defeats in four of their last five league fixtures at Goodison Park.
Ancelotti's team will certainly be looking to secure maximum points from their next two matches against Southampton and West Bromwich Albion ahead of a difficult trip to Chelsea on March 8, while they also have an FA Cup quarter-final with Manchester City to come next month.
The Toffees suffered a 2-0 defeat when they travelled to Southampton for the reverse game earlier this season, while the two sides played out a 1-1 draw at Goodison Park during the 2019-20 campaign.
Southampton, meanwhile, have not won in the Premier League since overcoming Liverpool at the start of January, suffering seven defeats in their last eight league fixtures.
A disappointing run of form has seen the Saints slide down the table into 14th position, now 10 points off the top six and only eight points clear of the relegation zone, level on matches with 18th-placed Fulham.
It is difficult to imagine Ralph Hasenhuttl's side being dragged into trouble at this stage but just five points separates them from 17th-placed Newcastle United, and it is not impossible to see how the strugglers could quickly become candidates for a potential shock relegation if their poor form continues.
Southampton have found it difficult on their travels this season, winning just three of their 12 matches, suffering five defeats in the process, but they can take confidence from Everton's issues at Goodison Park.
Everton Premier League form: LWDLLW
Everton form (all competitions): WDWLLW
Southampton Premier League form: LLLLDL
Southampton form (all competitions): LLWLDL
As for Southampton, William Smallbone, Michael Obafemi, Kyle Walker-Peters, Ibrahima Diallo and Theo Walcott are all unavailable through injury, while a thigh problem will see on-loan Liverpool attacker Takumi Minamino miss out.
Oriol Romeu looks likely to miss the remainder of the season due to a fractured ankle, meanwhile, with Hasenhuttl's side suffering a number of injuries at a key stage of the campaign.
Everton possible starting lineup:
Pickford; Holgate, Godfrey, Keane, Digne; Doucoure, Davies, Allan; Rodriguez, Calvert-Lewin, Richarlison
Southampton possible starting lineup:
McCarthy; Bednarek, Salisu, Vestergaard, Bertrand; Djenepo, Armstrong, Ward-Prowse, Tella; Ings, Adams
We say: Everton 2-0 Southampton
Southampton's injury problems could hardly have come at a worse stage of the season, and it is difficult to imagine the Saints returning to winning ways against Everton. The Toffees will be in confident mood following their win over Liverpool, and we fully expect Ancelotti's side to collect another three points here.
Watch the Sports Mole Football Shorts prediction for this game below: