The Scudetto holders beat Braga in midweek, but last week's loss to Juventus left them 14 points off the top of the table; meanwhile, Cagliari's climb away from the drop zone continues.
Match preview
Now into the Champions League knockout phase for a third season running, following Tuesday's 2-0 defeat of Braga at Stadio Maradona, Napoli are hoping to translate their continental form into better results in domestic competition.
Although Victor Osimhen's first-half strike, which followed an early own goal, secured second place in Group C behind Real Madrid, the Italian champions have lost their last two league matches without scoring and could now lose three on the spin in Serie A for the first time since January 2020.
A 2-1 victory over Atalanta BC in Walter Mazzarri's first match since returning as head coach bred some optimism in the camp, but three losses then followed, including two against title rivals Inter Milan and Juventus.
Khvicha Kvaratskhelia missed a sitter in last week's 1-0 reverse to Juve, which was symptomatic of how things have been going for last term's Serie A MVP and his underperforming teammates.
As a result, Napoli have sunk to sixth place in the standings, and rather than catching leaders Inter, their thoughts will instead be fixed on salvaging a top-four finish and a spot in next season's Champions League.
They have, though, picked up just one point from their last four Serie A home games, leaving them with the largest negative difference between points accrued at home compared to those obtained away across Europe's top five leagues.
While the Partenopei have posted a mere seven points from as many matches at the Maradona - compared to 17 on the road - they will be confident of overcoming their latest visitors, given past results between the two sides: they have been beaten just once in 24 league meetings with Cagliari, winning 16 and keeping 12 clean sheets.
Cagliari's sole success during that period came back in September 2019, but recent events could see them travel to Campania confident of causing a rare upset against their southern rivals on this occasion.
Yet another late, late show saw the Isolani steal maximum points from under Sassuolo's noses on Monday evening, as stoppage-time strikes from Gianluca Lapadula and super-sub Leonardo Pavoletti secured a 2-1 victory in Sardinia.
The latter - last season's Serie B playoff final hero - produced another improbable winner in the 99th minute, finding the net with an overhead kick after arriving from the bench. He had already bagged a last-gasp brace to see off Frosinone in October's seven-goal thriller.
No side has scored more times than Cagliari after the 85th minute of Serie A matches this season (six, level with Roma) and such never-say-die spirit has helped Claudio Ranieri's men move off the foot of the table into 16th place.
Having ended a run of three games without a win, Ranieri will now lead his troops to Naples, where the 72-year-old was once manager over three decades ago.
Napoli Serie A form:
D
W
L
W
L
L
Napoli form (all competitions):
L
W
L
L
L
W
Cagliari Serie A form:
W
W
L
D
L
W
Cagliari form (all competitions):
W
W
L
D
L
W
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Team News
Walter Mazzarri will still be without left-backs Mathias Olivera and Mario Rui on Saturday due to injury, but Norwegian defender Leo Ostigard should overcome an illness that kept him out of training after Napoli's midweek win over Braga.
Natan is set to continue as cover on the left side of the hosts' back four, although Alessandro Zanoli's recent return to fitness offers Mazzarri another option in that regard.
Starting up front, star striker Victor Osimhen has scored in each of his three league games against Cagliari and also struck for the first time since returning from injury on Tuesday evening.
As midfielder Antoine Makoumbou is back in the fold following suspension, long-term ACL absentee Marko Rog may be Cagliari's only man missing this weekend.
However, Peru international Gianluca Lapadula sustained a nose injury against Sassuolo and his place up front is in some doubt; Claudio Ranieri at least has several other forwards to choose from, with Zito Luvumbo, Eldor Shomorudov and Leonardo Pavoletti heading the queue.
A further option is ex-Napoli striker Andrea Petagna, who has scored four goals against his old club in Serie A with three different clubs - Atalanta, SPAL and Monza.
Napoli possible starting lineup:
Meret; Di Lorenzo, Rrahmani, Jesus, Natan; Anguissa, Lobotka, Zielinski; Politano, Osimhen, Kvaratskhelia
Cagliari possible starting lineup:
Scuffet; Zappa, Goldaniga, Dossena, Augello; Nandez, Makoumbou, Prati; Viola; Luvumbo, Petagna