Inter and Napoli go head-to-head at the top of the table, with Joaquin Correa partnering Lautaro Martinez against Victor Osimhen and Lorenzo Insigne.
It kicks off at San Siro at 17.00 GMT.
This becomes an even more important showdown for the Scudetto after Milan suffered their first defeat of the Serie A season, losing 4-3 at Fiorentina last night.
It means Inter have the opportunity to close the gap on the leaders, while Napoli can break away on their own at the top.
Stefan de Vrij and Alexis Sanchez picked up injuries on international duty and are out of action, so Andrea Ranocchia starts in defence.
Edin Dzeko is rested ahead of the Champions League, having sustained a minor muscular issue, so Tucu Correa partners Lautaro Martinez upfront.
Napoli have some concerns going to the Stadio Giuseppe Meazza, as Matteo Politano – a former Inter player – Diego Demme and Alessandro Zanoli have all tested positive for COVID-19.
Kostas Manolas and Adam Ounas are also injured, so Hirving Lozano gets the nod in the trident attack with Osimhen and Insigne.
Kalidou Koulibaly returns from suspension to bolster the defence.
The Partenopei debut the white version of their special edition Diego Armando Maradona kit, as next week marks a year since the icon’s death.
Inter: Handanovic; Skriniar, Ranocchia, Bastoni; Darmian, Barella, Brozovic, Calhanoglu, Perisic; Correa, Lautaro Martinez
Napoli: Ospina; Di Lorenzo, Rrahmani, Koulibaly, Mario Rui; Anguissa, Fabian Ruiz; Lozano, Zielinski, Insigne; Osimhen