Fresh off the back of a 4-0 demolition win at Stoke City in the FA Cup last weekend, the Foxes are now looking to kick on in the league to qualify for European football once again, but in particular their form at the King Power Stadium, where they have only won three times so far this campaign.
Ralph Hasenhüttl's Saints meanwhile have had extra time to prepare after their cup clash with Shrewsbury Town was called off last weekend due to a Covid-19 outbreak at their SkyBet League One opponents. However, will be full of confidence after their most recent fixture - a 1-0 win over current champions Liverpool - to put the South Coast outfit well and truly in the mix for a place in Europe next season.
Leicester will be without utility man Dennis Praet after manager Brendan Rodgers confirmed the Belgian will miss up to three months through injury.
The midfielder suffered a problem with his hamstring during last week's win, meaning that Hamza Choudhury could retain his place in this weekend's squad.
It's not all bad news for the East Midlanders though as Rodgers confirmed that Ricardo Pereira will be available, but won't be rushed back straight away.
The right-back has been recovering from a groin injury he picked up in his first appearance back after a nine-month spell out with an ACL injury but has progressed enough to be considered for selection.
Jamie Vardy and James Maddison will also be back in contention after they were rested as a precaution whilst Cengiz Under has also been deemed fit enough to play.
Southampton are not expecting star man Danny Ings to be available with the England international in self-isolation after testing positive for Covid-19.
One man who could return to the fold is goalkeeper Alex McCarthy after returning from self-isolation, however Hasenhüttl will have a dilemma following Fraser Forster's impressive display in-between the sticks against Liverpool.
Former Leicester transfer target Jannik Vestergaard and Moussa Djenepo are also expected to be doubtful for the game whilst combative midfielder Oriol Romeu is likely to be restored to the side after missing the Liverpool win with injury.
Leicester City XI: Schmeichel; Justin, Fofana, Evans, Castagne; Ndidi, Tielemans, Maddison; Barnes, Vardy, Albrighton.
Southampton XI: McCarthy; Walker-Peters, Bednarek, Stephens, Bertrand; Romeu, Armstrong, Ward-Prowse; Walcott, Long, Adams.
It was the visitors who were victorious when the two sides last met in January, coming from a goal behind to secure the three points just three months after suffering the embarrassing 9-0 defeat at the hands of the Foxes.
Dennis Praet opened the scoring in the 14th minute with his first goal for Leicester with a tidy close-ranged finish before Southampton equalised just five minutes later through Stuart Armstrong after the former Celtic man's deflected effort found the back of the net.
Danny Ings would then find the winner eight minutes from time, slotting the ball through the legs of Kasper Schmeichel as the Saints left the East Midlands having taken revenge for the heavy loss they endured earlier that season.
Ones to watch
Harvey Barnes - Leicester
The winger has gone from strength to strength this season with Leicester, scoring in three of his last four games in all competitions and his nine in total already matches his highest goal total for a campaign.
Barnes' decision making has vastly improved and as well as scoring, he is also creating chances for his teammates too. On current form he's one of the best players in the league and with his confidence evidently growing with each game that passes, the 23-year-old is expected to be the thorn in the Southampton side once again.
Che Adams - Southampton
Having been born in Leicester but not quite having made it at his local club, Che Adams will be keen to prove his doubters in the East Midlands wrong.
The former Birmingham City forward's task will be even greater as well with Southampton likely to be without their main talisman Ings and the pressure will be on the 24-year-old to fill the boots.
With just four goals from 16 appearances, Adams will need to be on top form and ensure he adds to his tally if Southampton are able to come away with the win.
Leicester boss Brendan Rodgers is well aware of the threats Southampton possess both as individuals and as a team and knows that his side will be coming up against an attacking side.
He said: “They’re very well organised. They want to play on the front foot and defend forward. It doesn’t surprise me. I’ve said before about the quality of the players they have.
"Alex McCarthy I know well, Ryan Bertrand is a Champions League winner, Walker-Peters has settled in very quickly, Stephens has come through and has acquitted himself well, he’s good on the ball, Ward-Prowse has great quality, Armstrong is a winner, Ings I know very well, his movement his terrific and he can finish. It’s not rocket science. They’re organised and with the quality, that makes them a very good team."
Saints boss Hasenhüttl meanwhile admitted he has huge admiration for the way Leicester have evolved after their famous 2015-16 title win.
"It's fantastic," he said. "Since they have become champions, this club was definitely developing and took advantage of this famous year they had.
"They have signed very good players and a very good manager, who is driven also by making this team better every day and this makes them strong. It is always tactically a very interesting game I think."
How to watch
The game will be shown live on BT Sport 1 and BT Sport 1 HD from 7:30pm with kick-off at the King Power Stadium getting underway at 8:00pm.
Live text updates are also available on the VAVEL website and Leicester VAVEL Twitter Page.