While the hosts have returned to Italy's top flight for the third time in 10 years, their first visitors stormed to the title last term; ending 33 years of hurt.
Match preview
Lifting the Scudetto for the first time since 1990 brought both relief and joy to the one-club city of Naples last season, as a scintillating Napoli side wrapped up top spot in Serie A with five games to spare.
Although a barnstorming start to the 2022-23 campaign began to falter in the spring, stars such as Khvicha Kvaratskhelia (12 goals and 10 assists in the league) and Victor Osimhen - who was crowned Capocannoniere after racking up 26 Serie A strikes - were ultimately rewarded for their brilliance; leaving runners-up Lazio and the rest of Calcio's big guns trailing in their wake.
After such a stellar campaign, in which they also suffered a disappointing Champions League exit to Milan after sprinting through the group stage, Napoli then lost their cherished coach Luciano Spalletti, who is now expected to cut short a sabbatical and take on the task of managing Italy.
Another ex-Roma boss, Rudi Garcia, was considered by many to be an underwhelming replacement, but the Partenopei's successful pre-season suggests they may be able to put up a reasonable defence of their title.
Having kept their star players, Bayern-bound Kim Min-jae aside, a club run on tight financial principles by Aurelio De Laurentiis has invested in some relatively modest signings, with Brazilian centre-back Natan replacing Kim and Reims midfielder Jens Cajuste brought in for around £10m.
Napoli rounded off their warm-up schedule with wins over Augsburg and Apollon Limassol, and they now tackle their first Serie A fixture having won each of their last six games on matchday one - already a club record.
In addition, the reigning champion of Italy has won their opening game in 10 of the last 11 years, while Napoli have never before lost their first Serie A fixture when facing a promoted side.
Such is the size of their task this weekend, Serie B champions Frosinone will host the Scudetto holders with some trepidation; having lost all four of the clubs' previous top-flight meetings Napoli, conceding 15 goals in the process.
As they prepare for their third crack at the big time in a decade, the Ciociari have also have lost each of their two previous openers: at home to Torino in 2015 and against Atalanta three years later.
After finishing last season seven points clear of second-placed Genoa to make their latest return, Frosinone suffered the blow of losing the architect of that success when 2006 World Cup hero Fabio Grosso stepped aside soon after promotion was sealed.
Former Roma and Cagliari boss Eusebio Di Francesco now occupies the Gialloblu's bench, and following an unbeaten pre-season, his reign started for real with a first-round victory in the Coppa Italia last week.
Securing a spot in the last 16, Frosinone saw off former Serie B counterparts Pisa thanks to an early own goal that separated the sides at Stadio Benito Stirpe.
However, with only a series of loan signings and free transfers bolstering the squad that won promotion, Di Francesco has his hands full to keep his new club afloat in the top flight - and Saturday's game will present a baptism of fire.
Frosinone form (all competitions):
Napoli pre-season form:
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Team News
For his first competitive match as Napoli head coach, Rudi Garcia is expected to name a familiar starting XI on Saturday, with Kim Min-jae's departure covered by either Leo Ostigard or Juan Jesus.
Therefore, goalkeeper Alex Meret should line up behind a 4-3-3 formation featuring captain Giovanni Di Lorenzo at right-back and last term's top scorer Victor Osimhen up front.
Only Andre-Frank Zambo Anguissa will miss Napoli's season opener through injury, but summer signing Jens Cajuste - who incidentally scored three Ligue 1 goals as a substitute this calendar year, before switching to Stadio Maradona - is still likely to start on the bench.
Frosinone, meanwhile, are set to select their own recent midfield reinforcement, with Abdou Harroui joining captain Luca Mazzitelli in a central trio.
After making his first-team breakthrough at Juventus last season, loanee Enzo Barrenechea is also available to coach Eusebio Di Francesco, who will turn to Gennaro Borrelli to lead his front three - last term's leading scorer Samuele Mulattieri has left for Sassuolo.
Frosinone possible starting lineup:
Turati; Oyono, Monterisi, Romagnoli, Marchizza; Gelli, Mazzitelli, Harroui; Baez, Borrelli, Caso
Napoli possible starting lineup:
Meret; Di Lorenzo, Rrahmani, Jesus, Olivera; Elmas, Lobotka, Zielinski; Politano, Osimhen, Kvaratskhelia