Leverkusen were beaten 3-2 at home by Leipzig before the international break, the first loss since May 2023 for the reigning league and cup champions.
While any defeat, particularly against a likely title rival, would have disappointed coach Xabi Alonso, the way in which it happened will be most concerning.
Just as they did in the Supercup against Stuttgart and in the league opener to Borussia Moenchengladbach, Leverkusen scored first but were pegged back.
But while Leverkusen rallied late to win both of those matches, they had no answer for a rampant Lois Openda, who scored twice in the second half to turn the match.
Known for late goals -- Leverkusen have scored 17 times in the 88th minute or later in 2024 -- Alonso's men were unable to salvage their record.
Having qualified for Europe last season, Hoffenheim are an unknown quantity this year. They beat the promoted Holstein Kiel in their opener but were outclassed by fellow Europa League side Eintracht Frankfurt the week after.
While the statement win over Leverkusen broke a stunning streak, Leipzig have quietly been putting together a run of their own.
Leipzig's last loss -- a 2-1 defeat at Bayern thanks to a stoppage time Harry Kane goal -- came in February, a 15-game unbeaten run.
They host Union Berlin on Saturday but will be without manager Marco Rose, who saw yellow twice in the win over Leverkusen.
Along with Leipzig, Bayern and unlikely league leaders Heidenheim are the only three clubs to have won two from two to start the season.
Bayern travel to Kiel on Saturday in just the second meeting between the two clubs. The first took place in the German Cup in 2021, when Kiel knocked Bayern out on penalties in the second round.
The exit kick started a run of poor performances in the German Cup; 20-time winners Bayern have not made it past the quarter finals for the past four years.
Despite leading the league, Heidenheim travel to Borussia Dortmund on Friday knowing the pressure is well and truly on their opponents.
Dortmund's limp scoreless draw at Werder Bremen last start has again put the spotlight on a side who, despite making the Champions League final last campaign, stumbled to fifth in the league.
Heideheim coach Frank Schmidt on Thursday backed his side to "make the impossible possible" against their heavily favoured opponents.
Dortmund can however count on the debut of striker Serhou Guirassy, who has returned from a knee injury.
Coach Nuri Sahin said Thursday Guirassy, who joined from Stuttgart in summer, had made an "excellent impression" this week.
One to watch: Benjamin Sesko (RB Leipzig)
After a disappointing goalless Euros for Slovenia, Leipzig striker Benjamin Sesko has laid on two assists and scored once in three games this campaign.
The forward made his lofty ambitions known this season, telling the Bundesliga website on Thursday "we want to be first. We want to win the league.
"Of course, it's really far away, but we believe we can do it."
Leipzig sporting director Marcel Schaefer told AFP and other media on Thursday "he's a complete striker... he's got everything a top striker needs."
"He's got everything and we want to help him achieve his potential."
Key stats
0 - League leaders Heidenheim and Friday's opponents Borussia Dortmund are the only two sides yet to concede a goal this season.
4 - Hoffenheim's Andre Kramaric has four goals in two games to start the league season.
15 - Leipzig have not lost since February in any competition, a run of 15 games.
Fixtures (1330 GMT unless stated)
Friday
Borussia Dortmund v Heidenheim (1830)
Saturday
Freiburg v Bochum, Wolfsburg v Eintracht Frankfurt, Borussia Moenchengladbach v Stuttgart, RB Leipzig v Union Berlin, Hoffenheim v Bayer Leverkusen, Holstein Kiel v Bayern Munich (1630)
Sunday
Heidenheim v Augsburg, Bayern Munich v Freiburg (1530)
