While the hosts are looking to boost their hopes of survival, the visitors are keen to turn their fortunes around as they endeavour to secure European football for next season.
Match preview
Sassuolo extended their unwanted winless run in Serie A to six games when they suffered a 3-2 home defeat to Empoli last weekend - their 15th league loss of the campaign.
The Neroverdi were on course to claim a precious point after Gian Marco Ferrari restored parity with his first goal of the season 13 minutes from time, but they were ultimately unable to hold on as Empoli snatched victory courtesy of a 94th-minute header from Simone Bastoni.
That result proved to be the final nail in the coffin for manager Alessio Dionisi, who was sacked by Sassuolo on Sunday after two-and-a-half years in charge. The 43-year-old leaves the club sitting 17th in the Serie A standings and only above the relegation zone on goal difference - level on points with Hellas Verona and Cagliari in 18th and 19th respectively.
Sassuolo youth team coach Emiliano Bigica has been placed in interim charge of the senior side and will hope to make an immediate impact on the training field in preparation for intriguing fixtures against an out-of-sorts Napoli side and fellow relegation-threatened duo Verona and Frosinone.
Success on Wednesday could prove challenging, though, as Sassuolo have only won two of two of their previous 21 Serie A encounters with Napoli, failing to score in any of their last three, while their home form also leaves little to be desired as they have picked up maximum points in only one of their last nine league games at the Mapei Stadium.
Since fighting back from a goal down to beat Verona 2-1 in their first match of February, Napoli have failed to win any of their last four fixtures in all competitions, drawing each of their last three by a 1-1 scoreline against Genoa, Barcelona and Cagliari.
Positives were taken from Napoli rescuing a draw against Barcelona in their Champions League last-16 first-leg tie a week ago, but they dropped two points in disappointing fashion in their Serie A clash with Cagliari last weekend.
Francesco Calzona was taking charge of his first Italian top-flight match after replacing Walter Mazzarri in midweek, but the former Slovakia national team boss was unable to lead his new side to victory as Victor Osimhen's 65th-minute opener was cancelled out by a 96th-minute equaliser from Zito Luvumbo.
It is fair to say that Napoli's Scudetto defence has not gone to plan this season, as they currently sit ninth in the table and a whopping 29 points behind leaders Inter Milan, while their hopes of securing Champions League football for next season are hanging by a threat as they are 11 points adrift of the top four with 13 games remaining.
Napoli will fancy their chances of returning to winning ways on Wednesday, though, as they have won each of their last four meetings with Sassuolo by an aggregate score of 14-1, including a 2-0 home victory at the beginning of this season.
Sassuolo Serie A form:
L
L
L
D
L
L
Napoli Serie A form:
W
D
W
L
D
D
Napoli form (all competitions):
D
W
L
D
D
D
Team News
Sassuolo are still having to cope without key attacker Domenico Berardi as he continues to recover from a knee injury, while Martin Erlic (muscle) and Mattia Viti (unspecified) will both be assessed ahead of kickoff.
Jeremy Toljan recovered from a hamstring problem to make the substitutes' bench last time out, and he will be pushing to return at right-back on Wednesday at the expense of Marcus Holmgren Pedersen.
Samu Castillejo will continue to battle with Cristian Volpato for a start on the right flank, while top scorer Andrea Pinamonti - who has nine league goals to his name this term - is set to lead the line.
As for Napoli, Cyril Ngonge has missed the last two games with a muscle strain and the winger is unlikely to be involved on Wednesday.
However, Giovanni Di Lorenzo is available to return after serving a one-match suspension last time out, and he is expected to take the place of Pasquale Mazzocchi at right-back, joining Amir Rrahmani, Juan Jesus and Mathias Olivera in the back four.
Matteo Politano will likely take the place of Giacomo Raspadori on the right side of attack, while Khvicha Kvaratskhelia keeps his spot on the left and Osimhen - who has scored in each of his last two appearances since returning from the Africa Cup of Nations - leads the line in the centre of the front three.
Sassuolo possible starting lineup:
Consigli; Toljan, Tressoldi, Ferrari, Doig; Henrique, Boloca; Castillejo, Thorstvedt, Lauriente; Pinamonti
Napoli possible starting lineup:
Meret; Di Lorenzo, Rrahmani, Jesus, Olivera; Anguissa, Lobotka, Zielinski; Politano, Osimhen, Kvaratskhelia