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In a volatile match which saw visiting coach Marco Rose sent to the stands in the first half, Leverkusen jumped out to a 2-0 lead thanks to goals from Jeremie Frimpong and Alex Grimaldo. But Kevin Kampl scored for Leipzig against the run of play just before half-time and Lois Openda levelled things up early in the second period.
Openda scored again with 10 minutes remaining to secure victory for Leipzig against last season's unbeaten league and cup winners.
"We had the chance to finish the game, but the goals we conceded were far too easy," said Leverkusen captain Jonathan Tah. "We defend as a team, but we fell asleep a few times and of course we're going to be punished."
The loss for Leverkusen ended a run of 43 domestic matches without defeat, a run spanning 463 days.
