Only Rob Holding and Henrikh Mkhitaryan retain their places from the 1-1 draw against Liverpool, with Carl Jenkinson making a first Arsenal appearance in Europe since a 2016 fixture against PSG.
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Mattéo Guendouzi returns in midfield after his domestic suspension, and he partners Aaron Ramsey in the centre of the pitch.
Elsewhere, Sokoratis returns after an ankle injury and partners Holding. Danny Welbeck leads the line with Alex Iwobi and Emile Smith Rowe in behind.
For Sporting, Nani captains the side with Fredy Montero leading the line.
Arsenal: Cech; Jenkinson, Holding, Sokratis, Lichtsteiner; Ramsey, Guendouzi; Iwobi, Smith-Rowe, Mkhitaryan; Welbeck. Subs: Martinez, Mustafi, Kolasinac, Torreira, Maitland-Niles, Aubameyang, Nketiah
Sporting: Ribeiro; Gaspar, Coates, Mathieu, Acuña; Nani, Miguel Luis, Gudelj, Bruno Fernandes; Diaby, Montero. Subs: Salin, Jefferson, Pinto, Mane, Petrovic, Dost, Cabral