A well-taken brace from Poland international Piotr Zielinski helped Napoli to a 4-1 win in Sardinia last time out, as the Partenopei stayed ahead of key rivals for Champions League qualification, such as Lazio, Atalanta and defending champions Juventus.
As they face Juve twice in the upcoming weeks - both in the league and the Supercoppa Italiana - coach Gattuso will have welcomed a less challenging start to the calendar year. After the fixtures against struggling Cagliari and now Spezia, Udinese, Empoli (in the cup) and Fiorentina are next to come.
The manager has a strong base to build on, as his side are now fourth in the standings and have a game in hand on those above them.
His well-drilled outfit can also boast the best defensive record in the top flight so far, with only 13 goals conceded and five clean sheets registered in the process.
Having racked up an incredible tally of 34 attempts at goal versus Cagliari, Napoli are also capable of carrying a significant threat at the other end.
With 63% possession at the Sardegna Arena and 93% pass accuracy, clearly they are very comfortable on the ball too and will expect to dominate against Spezia.
Furthermore, Napoli can also boast a perfect record against the Ligurian side in the top flight and have won all three games played between the two clubs to date.
Spezia's first ever Serie A campaign started on a positive note, with several impressive performances and surprise results. However, an ongoing downturn in fortunes has seen them slip into the relegation zone, level on points with Torino and Genoa.
In fact, Torino are the only club to have conceded more goals than Spezia so far, as the Aquilotti have let in two or more goals in 11 of their 15 league games.
Vincenzo Italiano's side are now winless in their last eight Serie A matches and lost to Verona last time out, after defender Julian Chabot was red-carded in the second half. Within minutes of his dismissal, the Gialloblu struck the game's only goal through Mattia Zaccagni.
One of the few rays of light for Spezia has been the form of striker M'Bala Nzola, as the previously unheralded French journeyman has scored seven goals in his first 11 top-flight appearances.
Such a rate places Nzola in exalted company, as the three most recent Serie A debutants to have scored seven or more goals so quickly were Krzysztof Piatek (nine for Genoa in 2018-19), Cristiano Ronaldo (seven, also in 2018-19) and Romelu Lukaku (seven, last season).
Italiano must hope his powerful forward is on song in Naples on Wednesday, as chances may be few and far between against an experienced opposition backline.
Napoli Serie A form: WWLLDW
Napoli form (all competitions): DWLLDW
Spezia Serie A form: LLDLLL
Gattuso will again be without defensive rock Kalidou Koulibaly as well as Dries Mertens and Diego Demme, while injured striker Victor Osimhen tested positive for COVID-19 following a Christmas trip to Nigeria and must quarantine.
Given the quick turnaround between games - with three in a week to start the year - Gattuso could opt for Alex Meret in goal and possibly offer a rare opportunity to summer signing Amir Rrahmani ahead of Nikola Maksimovic in defence.
After his red card at the weekend, Spezia are without the suspended Chabot, so Claudio Terzi should return to the centre of defence alongside Martin Erlic. Both Matteo Ricci and Simone Bastoni remain absent due to COVID-19 infection.
Coach Italiano also has midfielder Nahuel Estevez suspended, with Alessandro Deiola most likely to deputise. In attack, Diego Farias could return to the starting XI in place of goal-shy Kevin Agudelo, in support of star man Nzola.
Napoli possible starting lineup:
Meret; Di Lorenzo, Manolas, Rrahmani, Hysaj; Ruiz, Bakayoko; Lozano, Zielinski, Insigne; Petagna
Spezia possible starting lineup:
Provedel; Vignali, Erlic, Terzi, Marchizza; Deiola, Agoume, Maggiore; Gyasi, Nzola, Farias
We say: Napoli 3-1 Spezia
Expect Napoli to live up to their 'overwhelming favourites' tag at Stadio Diego Maradona, as Spezia are low on confidence plus diminished by illness and injury.
A further three points would maintain Gattuso's men as an outside shot for the Scudetto, so they should not let their focus slip against modest opposition.