The Bavarians have a gruelling fixture list of nine games in 29 days in April, including playing Real Madrid home and away in their mouth-watering Champions League quarter-final.
While Muller is ruled out against Hoffenheim, Bayern will be able to recall Spanish duo Javi Martinez and Xabi Alonso to the side after they served their suspensions. Bremen took a first-half lead when Zlatko Junuzovic's superb long ball was headed in by defender Theodor Gebre Selassie.
Chances were plentiful for Bayern Munich, but it was Andrej Kramaric who helped secure a dramatic win for Hoffenheim. "The win is unbelievable", Hoffenheim backer Dietmar Hopp said after his side's first ever victory over Bayern at the 18th attempt.
As Bayern pressed for an equaliser, both Lewandowski and Alonso had shots blocked in quick success - but Kramaric nearly snatched a second from a Steven Zuber through-ball.
Hoffenheim, who had never previously beaten Bayern in the league, are third with 51 and still on course for a Champions League place while Borussia Dortmund remain their closest rivals, remaining fourth after easing past Hamburg SV 3-0. We had our chances to level the scores.
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The Bundesliga leaders threw everything forward in the closing stages of the second half, but the host managed to hold on for an impressive three points.
Dortmund created a number of opportunities, but Rene Adler denied Aubameyang several chances to extend the lead.
The victory for Hoffenheim comes at a time when the club is riding a seven-game unbeaten streak.
Jojic scored his second goal in two games after picking up David Abraham's header outside the box before driving a shot past Lukas Hradecky and into the net via a post eight minutes into the second half. Ex-Dortmund midfielder Milos Jojic scored Cologne's victor in their 1-0 victory over Eintracht Frankfurt which moved his side up to fifth.