Napoli opt for Dries Mertens and Lorenzo Insigne together in the Europa League quarter-final, while Pierre-Emerick Aubameyang and Mesut Ozil start for Arsenal.
The first leg kicks off at the Emirates in London at 20.00 UK time (19.00 GMT).
Insigne has fully recovered after three weeks out with a thigh injury and starts alongside Mertens, leaving Arkadiusz Milik on the bench, as Carlo Ancelotti wants to use their pace and trickery to surprise the often-pedestrian Arsenal defenders.
Simone Verdi passed a fitness test, but is on the bench, while Elseid Hysaj and Mario Rui get the nod as full-backs.
Alex Meret is in goal, as Arsenal-owned David Ospina has not played since he collapsed following a knock to the head against Udinese on March 17.
Unai Emery has already won the Europa League three times with Sevilla, prompting Ancelotti to quip the Arsenal boss has “more experience” in this tournament.
There are several injury problems to deal with and Aubameyang – who grew up in the Milan youth academy – is available after completing a course of antibiotics and only being a substitute in the last two Premier League games.
Aaron Ramsey has already signed on to join Juventus next season and is in midfield, but while Laurent Koscielny does start, Granit Xhaka is not even fit enough for a place on the bench.
Mesut Ozil is given the nod behind Aubameyang and Alexandre Lacazette.
Former Milan and Genoa defender Sokratis Papastathopoulos starts in the three-man back line.
Ex-Sampdoria midfielder Lucas Torreira had a very strong start in the Arsenal jersey, but his form has fallen off in recent weeks.
There are some concerns ahead of the second leg, as Mario Rui, Xhaka and Henrikh Mkhitaryan are one yellow card away from suspension.
Arsenal:Cech; Papastathopoulos, Koscielny, Monreal; Maitland-Niles, Torreira, Ramsey, Kolasinac; Ozil; Aubameyang, Lacazette
Arsenal bench:Leno, Elneny, Mkhitaryan, Iwobi, Mustafi, Denis Suarez, Guendouzi
Napoli:Meret; Hysaj, Maksimovic, Koulibaly, Mario Rui; Callejon, Allan, Fabian Ruiz, Zielinski; Insigne, Mertens
Napoli bench:Ospina, Malcuit, Ghoulam, Chiriches, Ounas, Younes, Milik
Ref:Undiano Mallenco (ESP)
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