Lacazette may feel he can play in tandem with Pierre-Emerick Aubameyang , but Arsene Wenger is taking no chances with the French striker ahead of an important European clash with CSKA Moscow.
He, along with Ozil, may still be called to play, but Wenger will hope he can allow his Europa League stars to remain resting on the bench.
It's likely that 18-year-old Nelson will operate somewhere in a three-man line behind Aubameyang, with Alex Iwobi and Danny Welbeck completing the trio of support attackers.
Mohamed Elneny and Granit Xhaka are preferred to Jack Wilshere and Aaron Ramsey at the heart of midfield, while Hector Bellerin and Sead Kolasinac flank Calum Chambers and Shkodran Mustafi in defence.
Arsenal XI : Cech; Bellerin, Chambers, Mustafi, Kolasinac; Elneny, Xhaka; Iwobi, Nelson, Welbeck; Aubameyang
Subs : Macey, Holding, Monreal, Wilshere, Ozil, Lacazette, Nketiah
Southampton XI : McCarthy; Cedric, Stephens, Hoedt, Yoshida, Bertrand, Romeu, Tadic, Hojbjerg, Ward-Prowse, Long
Subs : Forster, Pied, Redmond, Sims, Boufal, Austin, Gabbiadini