Roma are expected to start Edin Dzeko supported by Lorenzo Pellegrini and Stephan El Shaarawy, while Napoli favour Dries Mertens to Victor Osimhen and Hirving Lozano.
It kicks off on Sunday at 19.45 GMT, click here for a match preview.
The Giallorossi make the trip without suspended Bruno Peres, plus injured Jordan Veretout, Henrikh Mkhitaryan, Juan Jesus and Nicolò Zaniolo.
Borja Mayoral played in the Europa League on Thursday and scored both goals in the 2-1 win over Shakhtar Donetsk.
The fact the team only returned to Rome on Friday morning suggests Mayoral will therefore be rested in favour of Dzeko.
El Shaarawy can also get the nod with Pellegrini, while Roger Ibanez has recovered after a knock to the head in Kiev.
Napoli’s injury crisis is finally beginning to ease, as only Andrea Petagna and Faouzi Ghoulam remain on the treatment table.
Stanislav Lobotka is in a clinic after is tonsillitis deteriorated, while full-back Giovanni Di Lorenzo is suspended, so Elseid Hysaj and Mario Rui complete the defence.
Although ex-Roma man Kostas Manolas does return, he is not expected to start.
Mertens is the favourite to play as centre-forward, with Lorenzo Insigne and Matteo Politano, leaving Victor Osimhen and returning Chucky Lozano initially on the bench.
Fabian Ruiz and Diego Demme are tipped to play in midfield rather than Tiemoue Bakayoko.
Roma: Pau Lopez; Mancini, Cristante, Ibanez; Karsdorp, Villar, Diawara, Spinazzola; Pellegrini, El Shaarawy; Dzeko
Napoli: Ospina; Hysaj, Maksimovic, Koulibaly, Rui; Ruiz, Demme; Politano, Zielinski, Insigne; Mertens
Ref: Di Bello