Napoli desperately need to get back on track with Kevin De Bruyne getting accustomed to his new role, while Roma bring back Donyell Malen amid an injury crisis.
It kicks off at the Stadio Diego Armando Maradona at 17.00 UK time (18.00 CEST).
This is a Scudetto showdown, although Napoli are a long way off the top spot after a dismal run of form, which culminated in a 3-1 defeat to rock bottom Venezia.
They lost two on the bounce between Serie A and the Champions League, before scraping a chaotic 4-3 victory over Bodo/Glimt in Europe on Tuesday with the first Scott McTominay goals of the season.
There’s no room for squad rotation, so Rasmus Hojlund, McTominay and Matteo Politano are confirmed, with De Bruyne again used in a deeper midfield role that he is not fond of.
Alisson Santos, David Neres, Costantino Favasuli and Alessandro Buongiorno are still out of action, bit Antonio Vergara returns to the bench.
Amir Rrahmani has been suffering from flu symptoms and is not even on the bench, but there were reports Vanja Milinkovic-Savic would be preferred to Alex Meret in goal and these are not confirmed.
Roma have their fair share of injuries too, Lorenzo Pellegrini limping off with a serious tendon strain during the 4-0 Champions League win over Slovan Bratislava.
He joins Paulo Dybala, Manu Koné and Mile Svilar on the treatment table.
Bryan Cristante made his comeback as a substitute after more than a month out in the midweek game, while Malen returns after missing the 2-0 win over Genoa through suspension.
Evan Ndicka and Gianluca Mancini were among those rested midweek, it looks as if Niccolo’ Pisilli is pushed into a more advanced role.
Roma have not beaten Napoli since a 2-0 home result in December 2023, managing three draws and two losses.
Their most recent victory in Naples was a 4-2 thriller in March 2018, followed by four stalemates and as many defeats.
Napoli-Roma line-ups
Napoli: Meret; Di Lorenzo, Marin, Badiashile, Olivera; Anguissa, De Bruyne, McTominay; Politano, Hojlund, Lang
Roma: Gollini, Mancini, Ndicka, Hermoso; Wesley, Cristante, De Roon, Rensch; Pisilli, Soulé; Malen
