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Ballon d'Or winner Dembele scored PSG's sixth just three minutes after coming on as a second-half substitute for his first appearance since suffering a hamstring injury in early September.
Desire Doue bagged a brace while Willian Pacho, Khvicha Kvaratskhelia, Nuno Mendes and Vitinha also hit the net at Leverkusen's BayArena as the visitors laid down the gauntlet to their European rivals.
Aleix Garcia scored both of the hosts' goals while PSG lost centre-back Illia Zabarnyi to a red card on 37 minutes, as he conceded a second spot-kick of the match, and Leverkusen had captain Robert Andrich dismissed for crashing his elbow into Doue's jaw a few minutes earlier.
PSG have been injury-hit and inconsistent this season, but once both teams were reduced to 10 men, they dominated their helpless hosts.
