Arsenal have been cruising in the continental competition with three wins in a four-game unbeaten run despite rotating their squad heavily. Wenger's men have already qualified for the knockout stages but a win in Germany would secure first place.
Basement club in the Bundesliga, Cologne are also bottom of the Europa League group, but Arsenal were made to come back from 1-0 down in the reverse fixture at the Emirates.
Theo Walcott could miss out through illness, while recoveries by David Ospine, Danny Welbeck and Olivier Giroud should see them make the cut. Reiss Nelson, Ainsley Maitland-Niles, Eddie Nketiah and Joe Willock could all be given the chance to impress.
Calum Chambers could also feature in a three-man defence, which could allow Wenger to restore Mohamed Elneny to a more natural midfield role, while Cologne vice-captain Jonas Hector is out due to a knee injury.
Cologne v Arsenal potential lineups:
Cologne: Horn, Klunter, Maroh, Mere, Rausch; Jojic, Lehmann, Ozcan, Osako; Guirassy, Cordoba.
Arsenal: Ospina; Chambers, Mertesacker, Holding; Nelson, Willock, Elneny, Maitland-Niles; Wilshere, Giroud, Welbeck.