Both clubs have faced major departures and upheaval this summer. With Felipe Anderson leaving for West Ham and Maurizio Sarri, along with Jorghnio heading for Chelsea. The new season will turn a new leaf as both clubs aim to put any summer woes behind them.
Lazio 1-4 Napoli (2017/18)
In what would turn out to be the first of two domestic drubbings at the hands of Napoli, Lazio suffered a second half obliteration that stunned the Stadio Olimpico into silence.
Despite a first-half opener from Stefan de Vrij, Napoli produced a rampant attacking display netting four times in the second period.
Most memorably a chip from Dries Mertens that made the rounds online was followed by a cheeky spot kick from Jorghino to top off a statement win.
Lazio: Jordan Lukaku and new signing Valon Berisha will both miss the game through injury. Right back Patric is also serving a suspension carried over from last season.
Simone Inzaghi has seen major parts of his team dismantled with Felipe Anderson, Stefan de Vrij and Federico Marchetti all gone, Lazio have tried to fill the gaps.
Joaquín Correa has been brought in from Sevilla to try and add a creative spark but keeping ahold of the much desired Sergej Milinkovic-Savic is probably Lazio's best bit of business.
Napoli: Right back Faouzi Ghoulam and winger Amin Younes are both missing through injury on opening day.
The direct replacement for Jorghino, Fabian Ruiz could make his start after joining from Real Betis. With Ancelotti still looking for a keeper to fill the boots of Pepe Reina, Orestis Karnezis is likely to start between the sticks on Saturday.
Although Napoli have a new manager, don't expect their style to change too radically..
For goals, Lazio will look toward Ciro Immobile again after his 29-goal haul last term. After losing Pepe Reina, Greek keeper Karnezis, bought from Udinese will be stepping in; potentially for the long term. Karnezis will have to prove doubters wrong against one of the most lethal forwards Serie A has to offer.
Sergej Milinkovic-Savic and Marek Hamšík will be two of the key figures in a crucial midfield battle. Milinkovic-Savic caught the eye of many in the World Cup and will hope to continue that form for his club. Hamšík, the ever-present in Naples, netted seven times last season, playing in every league game.
The two teams success on Saturday will depend on who takes control in the middle of the park.
Lazio (3-5-1-1): Proto; Radu, Acerbi, Cáceres, Marušić, Wallace, Badelj, Parolo, Correa, Milinković-Savić, Immobile
Napoli (4-3-3): Karnezis; Chiricheș, Maksimović, Mário Rui, Hysaj, Allan, Rog, Insigne, Hamšík. Fabián Ruiz, Milik
The major summer upheaval has severely halted both clubs progress from last season. New regimes, philosophies and players to gel could lead to a slow start.
However, both still have quality within their squads to trouble most teams within Italy's top tier and are likely to finish in similar positions to last season. For Lazio, a draw is probably the most realistic aim after conceding eight times in their two league meetings with Napoli last term.
Losing the creativity of Felipe Anderson will be difficult to replace in one window, and could leave them struggling for ideas up top.
'Sarrismo' was a revolution that swept across Naples, however the appointment of Ancelotti is a coup for Napoli. A CV that speaks for itself, plus the experience and winning mentality he has brought to many top clubs in Europe should bring its rewards.
With still the likes of Hamsik, Mertens and Callejón on their books, Napoli will still be too strong for Lazio on Saturday night.
Prediction: Lazio 0-2 Napoli