Napoli revolutionise the squad with Hirving Lozano and Arkadiusz Milik, sending Dries Mertens to the bench and Lorenzo Insigne the stands against KRC Genk.
It kicks off at the Luminus Arena at 17.55 UK time (16.55 GMT).
You can follow all the build-up and action as it happens from that game and Barcleona-Inter on the LIVEBLOG.
This is a very special match for Belgium international Dries Mertens, who is one goal off equalling Diego Armando Maradona’s tally of 115 in the Partenopei jersey, and former Genk defender Kalidou Koulibaly.
However, Carlo Ancelotti transforms his team with some shock decisions, as Mertens goes to the bench, Insigne and Faouzi Ghoulam are in the stands, making way for the all-new front pairing of Chucky Lozano and Milik.
According to Sky Sport Italia, Insigne is not injured, so this was purely a decision from the Coach.
Nikola Maksimovic and Elseid Hysaj did not make the trip due to injury, but Kostas Manolas has recovered from a muscular issue to start in defence.
KRC Genk are the Champions of Belgium, but sold many top stars over the summer and brought in a new Coach, son of Italian immigrants Felice Mazzù.
They are having some teething problems, as confirmed by the 6-2 defeat to RB Salzburg in this Champions League group.
There are also quite a few injuries leaving a very young squad, as Neto Borges and goalkeeper Danny Vukovic are unavailable.
Striker Dieumerci Ndongala was in doubt until the last minute with an ankle issue and is not even on the bench.
The biggest danger man is Tanzania international forward Ally Mbwana Samatta, with former Fiorentina youth player and son of legend Gheorge, Ianis Hagi.
Genk are not to be taken for granted, considering they have found the net at least once in 30 of their last 31 European fixtures.
Genk: Coucke; Maehle, Cuesta, Lucimi, Uronen; Berge, Hrosovsky, Bongonda, Hagi, Ito; Samatta
Genk bench: Vandeboordt, De Norre, Wouters, Dewaest, Heynen, Paintsil, Onuachu
Napoli: Meret; Di Lorenzo, Manolas, Koulibaly, Mario Rui; Callejon, Allan, Elmas, Fabian Ruiz; Lozano, Milik
Napoli bench: Ospina, Luperto, Malcuit, Zielinski, Younes, Mertens, Llorente
Ref: Kovacs (ROU)
Watch Serie A live in the UK on Premier Sports for just £11.99 per month including live LaLiga, Eredivisie, Scottish Cup Football and more. Visit: https://subscribe.premiersports.tv/