While the Foxes go into the game following defeat to English champions Manchester City, their Neapolitan visitors were able to beat old rivals Juventus with a late goal which preserves their perfect Serie A record.
Despite their disappointment at narrowly missing out on the continent's top competition for a second successive season, Leicester ended last season fifth in the Premier League - enough to earn them direct entry into the Europa League's group stage.
While the FA Cup winners exited last term's tournament in the last 32 - losing 2-0 on aggregate to Slavia Prague - it was still their best-ever result in either the UEFA Cup or Europa League.
To surpass that this autumn will be no mean feat, though, as after the Foxes get their Group C challenge under way at the King Power Stadium this week, they will face Polish champions Legia Warsaw next and then meet Spartak Moscow on October 10th.
In the run-up to their first-ever encounter with Italian opponents in UEFA competition, the side managed by Brendan Rodgers have experienced an up-and-down start to the new league season, as they have both won and lost twice so far and sit ninth in the early-season table.
Though Leicester took care of newly-promoted Norwich City just before the international break, they were edged out by Bernardo Silva's strike for Manchester City in an entertaining game at the weekend, as former City goalkeeper Kasper Schmeichel did well to prevent a greater margin of defeat.
The great Dane may be called upon again in midweek, as Rodgers and company now come up against one of the most consistent attacking forces on the continent.
Goals from Matteo Politano and star centre-back Kalidou Koulibaly gave Napoli a precious 2-1 win over loathed rivals Juventus at the weekend, and continued their run of fine form under new manager Luciano Spalletti.
Koulibaly's 85th-minute strike sealed a comeback win for the Azzurri, and helped them into third in the early Serie A standings - giving them a major boost before their return to the Europa League, after an underwhelming exit last term.
Much like Leicester, the Partenopei topped their group but were eliminated in the last 32 and, incidentally, both clubs then went on to finish fifth in their domestic leagues after missing out on Champions League qualification on the final day.
Knocked out by European debutants Granada last spring, an aggregate result which perhaps marked the beginning of the end for their colourful former coach Gennaro Gattuso, the Neapolitan giants are intent on going far further this time around - in keeping with their proud European history.
In Europe's second-tier club competition, they have progressed as group winners on each of their last three participations, including 2015-16 when they won all six matches and set a record for the most goals scored in a Europa League group (22).
In all, they are unbeaten in their last seven Europa League group stage fixtures on the road, winning five in a row before drawing 1-1 at AZ on the fifth matchday in 2020.
And Napoli's pedigree at this level is confirmed by their status as one of only five clubs involved this year that lifted the trophy in its former guise as the UEFA Cup, in a Diego Maradona-inspired run to glory back in 1989.
Ahead of Thursday's game, Napoli are expecting to be without captain Lorenzo Insigne, who was forced off in the second half versus Juventus. The Italy forward limped from the pitch after taking a set-piece, having already started the match with a bruised knee.
His international teammate, goalkeeper Alex Meret, was sent home from the Italian camp after sustaining a back injury and remains sidelined this week. Former Arsenal stopper David Ospina will therefore start.
Luciano Spalletti also has Stanislav Lobotka out with a muscular injury and Diego Demme is absent too. In the midfield department, then, new acquisition Andre-Frank Anguissa - who made a successful debut on Saturday - could join Fabian Ruiz and Eljif Elmas.
Leicester boss Brendan Rodgers has a number of selection headaches to resolve himself, as Ricardo Pereira was only fit enough to be an unused substitute at the weekend and Timothy Castagne may be therefore be set to continue.
Centre-back Jannik Vestergaard is still returning to full fitness, but after managing to complete an hour against Manchester City could get the nod once more, while Filip Benkovic has been registered in the Europa League squad and may be involved at some stage.
There have been calls for Rodgers to drop playmaker James Maddison after a run of 15 games without a goal or assist, so Patson Daka or Kelechi Iheanacho - who have both impressed in their limited time this season - may start in attack.
Leicester City possible starting lineup:
Schmeichel; Castagne, Vestergaard, Soyuncu, Bertrand; Albrighton, Tielemans, Ndidi, Barnes; Daka, Vardy
Napoli possible starting lineup:
Ospina; Di Lorenzo, Manolas, Koulibaly, Rui; Anguissa, Elmas, Ruiz; Politano, Osimhen, Lozano
We say: Leicester City 2-2 Napoli
An open game is in prospect on Thursday night, as both sides prefer to go forward and are usually capable of slicing open even the tightest defences.
Though Leicester have stuttered in the final third of late, the bright lights of a European night - and perhaps a change of attacking personnel - can help them secure a draw against their toughest Group C opponents.