Hoffenheim find themselves just three points clear of the bottom three in the Bundesliga table, while Leverkusen sit five points above the Baden-Wurttemberg outfit.
Match preview
When Hoffenheim flew out of the blocks at the start of the season - winning four of their first six Bundesliga games - it looked as though the Sinsheim club would mount a serious challenge for a European spot.
However, Hoffenheim have managed to win just one of their 13 league matches since then, registering four draws and eight losses along the way.
A nine-game winless run ultimately cost Breitenreiter his job, as Hoffenheim recorded two draws and seven defeats between October and February, with last weekend's 5-2 thrashing at VfL Bochum proving to be the final nail in the coffin.
It remains to be seen whether Pellegrino Matarazzo has got what it takes to turn the tide at the PreZero Arena, given that the American was only relieved of his duties as VfB Stuttgart boss back in October.
Hoffenheim have conceded at least two goals in each of their previous eight league defeats, allowing Borussia Monchengladbach to win 4-1 before last weekend's rout at Bochum, so Matarazzo must address the team's defensive issues before anything else.
It is worth remembering that Bayer Leverkusen have also switched managers this season, with Xabi Alonso replacing Gerardo Seoane in October following a run of one victory in eight matches.
After overseeing a 4-0 thrashing of Schalke 04 in his first game in charge, Alonso took a solitary point from the next three outings, but the Spaniard soon endeared himself to the Leverkusen faithful by inspiring a five-game winning streak in the Bundesliga.
Die Werkself beat Union Berlin, FC Koln and Stuttgart in the lead-up to the World Cup before defeating Gladbach and Bochum after the break, scoring a total of 14 goals in the process.
However, Leverkusen have taken a turn for the worse in recent weeks, suffering a 2-0 defeat to Borussia Dortmund before losing 1-0 to Augsburg last time out, so they will be eager to return to winning ways this weekend.
Given that Leverkusen have drawn just one of their previous 12 Bundesliga games - recording six wins and five losses along the way - it is difficult to predict how Alonso's men will perform at the moment.
Hoffenheim Bundesliga form:
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D
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Hoffenheim form (all competitions):
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D
L
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L
Bayer Leverkusen Bundesliga form:
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W
L
L
Bayer Leverkusen form (all competitions):
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L
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W
L
L
Team News
Pavel Kaderabek missed last weekend's 5-2 thrashing at Bochum, meaning that Christoph Baumgartner is expected to continue at right-wing back for Hoffenheim.
The hosts will also be without the injured quartet of Jacob Bruun Larsen, Grischa Promel, Kevin Vogt and Robert Skov on Saturday.
Naturally, Matarazzo will look to implement his ideas as quickly as possible when he takes to the PreZero Arena dugout for the first time, but he will also be wary of making too many changes.
As for Bayer Leverkusen, Patrik Schick, Charles Aranguiz and Andrey Lunev remain sidelined due to injury, while there are question marks over the fitness of Sardar Azmoun and Nadiem Amiri.
With eight goals and five assists to his name this season, Moussa Diaby is Leverkusen's danger man in attack, while Jeremie Frimpong has chipped in with five goals and three assists from right-back.
Hoffenheim possible starting lineup:
Baumann; Kabak, Brooks, Nsoki; Baumgartner, Geiger, Delaney, Tasende; Bischof; Bebou, Dolberg
Bayer Leverkusen possible starting lineup:
Hradecky; Kossounou, Tapsoba, Hincapie; Frimpong, Palacios, Andrich, Bakker; Diaby, Hlozek, Adli
We say: Hoffenheim 2-2 Bayer Leverkusen
Buoyed by the arrival of a new manager, the Hoffenheim players are bound to up their game in order to impress Matarazzo, but they could struggle to claim all three points on Saturday.
Although Bayer Leverkusen have lost each of their last two Bundesliga matches, they have won five of their previous seven, meaning that they will confident of avoiding defeat at the PreZero Arena.