One of six sides locked on seven points at the top of the Serie A standings, the Partenopei take on southern rivals who are yet to taste victory since promotion.
Match preview
Concluding Serie A's third round under the lights at Stadio Artemio Franchi, Napoli saw their lightning start to the season somewhat curtailed by an organised Fiorentina side, who posted their third straight goalless draw.
After lashing in nine goals during their first two matches - against Verona and Monza - Luciano Spalletti's side were denied a breakthrough despite fielding several newly-acquired attacking stars.
Nonetheless, the additions of Giovanni Simeone and Giacomo Raspadori to an already potent front line should pay dividends in the longer term, and will represent a fearsome prospect for Lecce to face in midweek.
Though their scoring streak of 15 successive away matches is now at an end, Napoli return to their Campanian headquarters, where they found the net at a rate of nearly two goals per game last term and put four past Monza on their most recent outing.
While generally having the upper hand against Wednesday's visitors historically, when the clubs last met in Serie A - back in February 2020 - it was Lecce who came out on top: winning 3-2 in Naples.
Such a result this time would be a blow to Spalletti's hopes of finally getting his hands on the Scudetto, and with games against Lazio and Liverpool to come in the next few days, Napoli will want to take care of business at home to more modest opponents.
Still seeking the first point of their Serie A comeback campaign, Lecce welcomed Empoli to Stadio Via del Mare on Sunday, and despite falling a goal behind to their Tuscan counterparts were able to fight back for a 1-1 draw.
Marco Baroni's men had been heading towards half time with a one-goal deficit, but Gabriel Strefezza's 40th-minute strike levelled the scores and ultimately got his team off the mark for the 2022-23 season.
Beaten with the last kick by Inter on the opening day, and then edged out by Sassuolo, the Puglian side have at least put a point on the board, but with just two goals so far they may need to up their attacking intent.
Last season's Serie B champions also crashed out of the Coppa Italia to Cittadella at the start of August, so a long slog against returning to the second tier is apparently all that remains - but a recent arrival has renewed hope among the Giallorossi faithful.
World Cup-winner Samuel Umtiti was greeted as a hero after completing his loan move from Barcelona last week; being reduced to tears by the Lecce fans' fervour.
Having taken his place on the bench against Empoli, the Frenchman's presence may be required in the back four at Stadio Maradona, given the hosts' countless options in the final third.
Napoli Serie A form:
Napoli form (all competitions):
Lecce Serie A form:
Lecce form (all competitions):
Team News
After keeping a settled side for the first three matches, tougher tests ahead may force Luciano Spalletti's hand into making changes on Wednesday evening.
Hirving Lozano's place in Napoli's front three is under particular threat, with Matteo Politano offering an obvious alternative, or a reshuffle could see new boys Giacomo Raspadori and Giovanni Simeone drafted into the lineup.
Tanguy Ndombele also made his debut from the bench in Florence, but looked a little off the pace. The French midfielder is likely to feature again, though, as Diego Demme is sidelined with a broken foot and Fabian Ruiz seems bound for Paris Saint-Germain.
Lecce, meanwhile, may decide to throw Samuel Umtiti in at the deep end, as they hope to benefit from his experience against top opposition - particularly as defensive duo Mert Cetin and Kastriot Dermaku are still struggling with injuries.
Should Marco Baroni decide against such a move, another recent signing, Marin Pongracic, should continue in the visitors' back four.
Up front, Federico Di Francesco and Milan loanee Lorenzo Colombo will hope to be given a chance to impress, with the current front three only mustering two goals between them so far.
Napoli possible starting lineup:
Meret; Di Lorenzo, Kim, Rrahmani, Rui; Anguissa, Lobotka; Politano, Raspadori, Kvaratskhelia; Osimhen
Lecce possible starting lineup:
Falcone; Gendrey, Baschirotto, Pongracic, Gallo; Bistrovic, Hjulmand, Gonzalez; Strefezza, Ceesay, Di Francesco