Wilshere is fit again after suffering a broken leg while on loan at Bournemouth last term.
And the 25-year-old could make his first appearance for Arsenal in 13 months if he gets on the pitch.
Arsene Wenger has made nine changes to his starting XI.
Nacho Monreal and Hector Bellerin are the two players to retain their places from Saturday’s win against Bournemouth.
David Ospina, Per Mertesacker, Rob Holding, Mohamed Elneny, Ainsley Maitland-Niles, Alex Iwobi, Theo Walcott and Olivier Giroud are given a run out.
Alexis Sanchez also starts in a bid to build up his fitness.
Wenger has shuffled the pack with one eye on Sunday’s Premier League clash with Chelsea.
Arsenal fans will have to wait an extra hour for the game, however, because the game has been delayed until 9.05pm due to crowd congestion.
Riot police entered the Emirates Stadium after Cologne fans sparked trouble after being let into the ground.
FOLLOW LIVE COVERAGE OF ARSENAL'S EUROPA LEAGUE CLASH WITH COLOGNE
Arsenal: Ospina, Mertesacker, Holding, Monreal, Bellerin, Elneny, Maitland-Niles, Iwobi, Walcott, Sanchez, Giroud
Subs: Macey, Wilshere, Mustafi, Reine-Adelaide, Kolasinac, Akpom, Nelson
Cologne: Horn, Heintz, Hoger, Zoller, Hector, Cordoba, Bittencourt, Mere, Klunter, Lehmann, Rausch
Subs: Kessler, Sorensen, Risse, Jojic, Osako, Guirassy, Horn
