The Italians, who lifted the trophy back in 1989 when it was known as the UEFA Cup, dropped down to this season's competition after being beaten by Athletic Bilbao in Champions League qualifying.
In contrast, Sparta Prague currently sit in second spot in their domestic league thanks to four wins from their opening seven games.
The Czechs had to beat Dutch side PEC Zwolle to make it through to the group stage of the Europa League, but a 4-2 aggregate victory saw them through safely.
Sparta Prague: DLWWWD
Possible starting lineups
Napoli: Rafael; Maggio, Albiol, Koulibaly, Zuniga; Inler, Jorginho; Callejon, Hamsik, Insigne; Higuain
Sparta Prague: Bicik; Kovac, Brabec, Nhamoinesu, Vacek; Matejovsky, Dockal, Marecek, Krejci; Kaderabek, Lafata
Sports Mole says: 2-0