The visitors have made an immediate return to this stage of the competition following last season's debut, whereas their hosts are making their fourth appearance at this juncture.
The clubs have been paired once before in UEFA competition, APOEL defeating Dudelange 1-0 both home and away in the second qualifying round of the 2017/18 UEFA Champions League. It was the first time Dudelange had lost both games in a two-legged European tie for five years, and they have not done so since.
Those are APOEL's only previous encounters with opposition from Luxembourg and Dudelange's sole experience against a Cypriot club.
APOEL and Dudelange are their respective countries' sole representatives in Europe this autumn.