The Bundesliga side have parted company with Breitenreiter after seven months in charge following a 5-2 defeat in Bochum on Matchday 19.
The Sinsheim outfit announced that the 49-year-old would be leaving the club on Monday, two days after the defeat in Bochum.
"We were able to sign a coach in Andre who didn't just have great acceptance in the team from the first day but also with all the backroom staff, our employees in the club offices, as well as all the fans and partners. We'd like to thank him for the good work together and many positive moments, especially at the start of our time together," said director of first-team football Alexander Rosen.
Breitenreiter took the helm in Hoffenheim in summer 2022 on a two-year deal and enjoyed a good start, guiding the club up to fourth place at the end of Matchday 10.
However, a run of nine Bundesliga matches without a win, stretching back to 14 October, has left the side down in 14th and just three points clear of the bottom three. Hoffenheim will now prepare for life without the former Schalke and Hannover coach.
Breitenreiter won five Bundesliga games in total during his 19-match spell in charge of the club.
Watch: Highlights of Hoffenheim's 5-2 loss at Bochum
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