The Sardinians are eight points from safety and have not won in 10 games, while Napoli will be boosted by their recent victories over Fiorentina and Wolfsburg.
There are no teams in the Italian top flight in worse form than Cagliari, who are without a league win in their previous 10 matches.
It has left them in 19th place in the league table and eight points from safety, with relegation starting to look increasingly likely.
Their woeful run led to Gianfranco Zola being dismissed as manager last month, but even the arrival of former boss Zdenek Zeman has failed to spark a revival and they have lost three of their four games under him.
Finding the back of the net is not usually a problem for them and they are among the highest scorers in the bottom half of the table, but they have shipped a huge 58 goals, which is the worst of any club in the top flight this season.
Recent form: LLDLLL
A season that had looked like ending in disaster for Napoli has been completely transformed in the space of a week.
They had gone into their league meeting with Fiorentina last Sunday without a win from their previous five Serie A games and after suffering a heartbreaking exit in the semi-finals of the Coppa Italia to Lazio.
However, they bounced back in style to claim a resounding 3-0 win over the Viola that moved them above the Florence outfit in the table and reignited their fading Champions League hopes.
It got even better for Rafael Benitez's side on Thursday evening, as they stunned Wolfsburg with a clinical display of attacking football to earn a 4-1 win over the Germans in the first leg of their Europa League quarter-final.
They have now been installed as the tournament favourites and it would take a major collapse to see them knocked out when the teams meet again in Naples next week.
Winning the Europa League may prove to be their best chance of getting into the Champions League next season, as they are currently seven points behind third-placed Roma, who occupy the final qualifying spot.
Lazio are eight points ahead of them and with those teams meeting on the last day of the campaign, Benitez will want his side to get as close as possible to the Rome outfit to give themselves a real shot of finishing inside the top three.
Recent form in Serie A: LDLDLW
Recent form (all competitions): DDLLWW
Cagliari are without the suspended Lorenzo Crisetig, who picked up a booking in last weekend's defeat to Genoa.
With the second leg of their match against Wolfsburg to come next Thursday, Benitez is likely to rotate his squad, meaning that the likes of Ivan Strinic and Jonathan de Guzman will be pushing for starting spots.
Cagliari possible starting lineup:
Brkic, Balzano, Rossettini, Diakite, Avelar, Dessena, Conti, Ekdal, Farias, Sau, M'Poku
Napoli possible starting lineup:
Andujar, Maggio, Albiol, Koulibaly, Strinic, Inler, Gargano, Callejon, Hamsik, De Guzman, Higuain
Head To Head
Six goals were shared when the teams met in this season's reverse fixture, as Cagliari came from behind to earn a 3-3 draw at the Stadio San Paolo.
This is a game that tends to produce plenty of excitement, as there have been a whopping 26 goals scored in the previous six matches between the teams.
It's Napoli who have the better head-to-head record in recent meetings and they are unbeaten in 11 games against the Sardinians.
We say: Cagliari 1-3 Napoli
Napoli look to have returned to form and their displays over the past week have been of the highest quality. They will be desperate to maintain their good run and against a Cagliari side who are short of confidence, we think that they will come away from Sardinia with all three points.