Aquilotti can finish no lower than 16th in the table, while Gli Azzurri have battled for the title this term but are guaranteed to finish third.
It ended a streak of four successive defeats for Thiago Motta's side, a run which had led to them looking nervously over their shoulders at the bottom three.
A win on Sunday would see Aquilotti equal their points tally of 39 from last season, which was their first-ever campaign in the top flight.
However, Spezia have lost their last three home matches and have only won five times all season at Stadio Alberto Picco.
Motta – who was only appointed last summer – is expected to depart for pastures new this summer and has surprisingly been linked with the Paris Saint-Germain job, while Andrea Pirlo has been tipped to replace him in Liguria.
Napoli were only one point off the Serie A summit six weeks ago, but they then picked up just one point from their next three games and have been left to watch from afar as the two Milan clubs battle it out for the title on the final day.
Nonetheless, Luciano Spalletti's first season in charge can still be considered a relative success and it will bring their highest finish in three years.
Gli Azzurri have recovered from their blip in April and have won their last three matches, with Victor Osimhen, Lorenzo Insigne and Stanislav Lobotka all netting in a 3-0 triumph over Genoa last weekend.
Over half of Napoli's points in Serie A this season have come away from home and they have only lost twice on the road all term. They have the joint-best defence in the league, having conceded just 31 goals in 37 games.
A Juan Jesus own goal gave Spezia a 1-0 victory at Stadio Diego Armando Maradona earlier in the season, which was only their second win over Napoli in nine meetings this century.
The season is over for Emmanuel Gyasi, who picked up his 10th yellow card of the campaign last weekend so is suspended.
Ebrima Colley, Leo Sena and Petko Hristov are all major doubts for the fixture, having been absent through injury in recent games.
Lorenzo Insigne will play his 434th and final game for Napoli before he joins Toronto FC this summer and ends a 16-year association with the Italian club.
Victor Osimhen's goal last weekend was his 14th in Serie A this season – his best tally for a league campaign in his career.
Spezia possible starting lineup:
Provedel; Amian, Erlic, Nikolaou, Ferrer; Maggiore, Kiwior; Verde, Agudelo, Kovalenko; Manaj
Napoli possible starting lineup:
Ospina; Di Lorenzo, Rahmani, Koulibaly, Ghoulam; Demme, Lobotka; Lozano, Mertens, Insigne; Osimhen
We say: Spezia 0-2 Napoli
Napoli are ending the campaign in good form and depending on how strong Luciano Spalletti decides to go with his team selection, they should finish with three points here. With their survival confirmed, Spezia are unlikely to provide that much of a challenge.
For additional data used by our team to analyse our suggested result please click here.