Bundesliga champions Bayer Leverkusen suffered their first Bundesliga defeat since May 2023 as a 3-2 loss at home to RB Leipzig on Saturday snapped their 35-match unbeaten run in the top flight.
Bayern face Freiburg, who have won only once in 17 previous meetings.
Every team will play eight games against eight different opponents in the new format of Europe's elite club competition, with all 36 clubs now pooled together into one league rather than split into groups.
Andrej Kramaric scored in the final minute of regular time to snatch Hoffenheim a 1-1 draw at home to 10-man RB Leipzig in the Bundesliga on Friday.
Fourth-placed Leipzig sit two points clear of Dortmund in fifth, with only the top four clubs guaranteed Champions League football next season.
A goal and an assist from Xavi Simons and a Lois Openda brace helped RB Leipzig thump Cologne 5-1 away on Friday to leapfrog Borussia Dortmund into the top four.
Real Madrid scraped through into the Champions League quarter-finals with a 1-1 second-leg draw against RB Leipzig on Wednesday, progressing 2-1 on aggregate.
Harry Kane scored two goals in the second-half, including an injury time winner, to snatch Bayern Munich a 2-1 home win over RB Leipzig on Saturday
Struggling Bayern Munich's shock decision to part ways with coach Thomas Tuchel at the end of the season will be put to the test in Saturday's clash with RB Leipzig.
An incredible solo goal from Brahim Diaz secured Real Madrid a 1-0 win away at RB Leipzig in Tuesday's Champions League last 16 first leg.
Jude Bellingham is also likely to miss league clashes with Rayo Vallecano, Sevilla and Valencia.
Leverkusen coach Xabi Alonso jumped with joy, securing a valuable three points against a top-four rival, although second-placed Bayern Munich have played two games fewer.
Four points behind with a game in hand, Harry Kane's Bayern are hovering dangerously close to a Leverkusen side hoping to break through for a first ever league title.
Despite topping their Champions League group, Borussia Dortmund have won just one of seven league games since October.
Leaders Bayer Leverkusen retain their three-point cushion and travel to third-place Stuttgart on Sunday on a weekend when six of the Bundesliga's top seven face each other.
Although only two points ahead of a Harry Kane-powered Bayern Munich, Leverkusen are already a whopping ten points in front of Borussia Dortmund.
Manchester City have now won 27 of their last 29 Champions League home games since they last tasted defeat.
With 31 of a possible 33 points from 11 games, Bayer Leverkusen have equalled the greatest start in Bundesliga history.