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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.
Xabi Alonso’s side, who have scored 17 goals in the 88th minute or later this year, pushed to keep their record alive, but could not find an equaliser this time.
“We knew it was going to be very hard to play here, Leverkusen play lethal football. We wanted to be courageous and get on the front foot,” said Kampl.
“We know we’ve also got quality up front. We were ice-cold today.”
Rose was sent to the stands after he was yellow-carded twice in quick succession in the first half for touchline outbursts after a foul on his player.
The Leipzig coach appeared to still be seething after Leverkusen striker Victor Boniface caught the head of Amadou Haidara while attempting a bicycle kick. He was upset Boniface escaped with a booking as Haidara needed to be replaced.
– Dortmund held at Bremen –
Earlier on Saturday, a toothless and ill-disciplined Borussia Dortmund were held to a 0-0 draw at Werder Bremen.
Dortmund dominated possession but failed to break through and played the final 17 minutes a man down after centre-back Nico Schlotterbeck was sent off.
They came into the game with Maximilian Beier as their one recognised striker, having sent Sebastien Haller out on loan to La Liga side Leganes late on Friday.
Summer signing Serhou Guirassy, brought in to replace Niclas Fuellkrug after the Germany striker left for West Ham, is still weeks away from a return from a knee injury.
Schlotterbeck picked up a second yellow for a challenge on Justin Njinmah, reducing his side to 10 men.
“Everything isn’t exactly great yet,” said Dortmund midfielder Pascal Gross. “The coach prepared us well but we need to do better at implementing it”.
Last season’s surprise runners-up Stuttgart again gave away points from a winning position, drawing 3-3 with Mainz after conceding an equaliser in stoppage time.
Strikes from Enzo Millot and Jamie Leweling inside the opening 15 minutes put Stuttgart in control.
The hosts however let Mainz back into the match when Millot gave away a clumsy penalty late in the first half which was converted by Nadiem Amiri.
Jonathan Burkardt, who won the penalty, headed Mainz level after 62 minutes.
Stuttgart – who led in their Bundesliga opener and in the Super Cup against Leverkusen before losing both — led again when Fabian Rieder scored a stunning free-kick with two minutes remaining.
Mainz’s Maxim Leitsch scored in the fourth minute of added time to snatch a point for the visitors.
“We actually played a pretty good game, but we undid it by making simple mistakes,” Stuttgart’s Angelo Stiller told Sky.
Eintracht Frankfurt won their opening home game 3-1 against Hoffenheim.
Frankfurt forward Hugo Ekitike again impressed in the win, scoring the opener and laying on a perfect pass for Hugo Larsson’s second.
Hoffenheim’s Andrej Kramaric, who scored a hat-trick in last week’s season opener, pulled one back for the visitors early in the second half but Egypt winger Omar Marmoush added another to seal the match.
Borussia Moenchengladbach won 2-0 at Bochum, while top-flight newcomers Holstein Kiel are still looking for their first Bundesliga point, going down 2-0 at home to Wolfsburg.
