The two sides served up a genuine contender for game of the season the last time they met on Matchday 3, but what's in store this time? bundesliga.com takes a look...
Bremen start the weekend as one of the Bundesliga's form sides, having moved five points clear of the relegation zone following three straight wins. Fifth-placed Leverkusen are steering a course for Europe, but as things stand would have to make do with a place in the UEFA Europa League.
Set-piece specialist Zlatko Junuzovic is available again following suspension and while fellow midfielder Philipp Bargfrede has been passed fit, winter signing Jannik Vestergaard (foot), Fin Bartels and leading scorer (thigh) are all doubts.
Heung-Min Son is set to make his return to the starting line-up after helping South Korea to a second-placed finish at the Asian Cup. Defenders Emir Spahic and Ömer Toprak and influential winger are touch-and-go, but Swiss striker Josip Drmic should at least make the bench.
If Di Santo does indeed miss out, the onus will be on young to fire his side to victory. The nimble 20-year-old is enjoying his breakthrough season in the Bundesliga, grabbing four goals and laying on three assists in ten league starts so far this term.
returns to the domestic scene having been given an extended break in the wake of his Asian Cup exertions Down Under. The South Korean forward hasn't scored in the Bundesliga since 22 November, but will doubtless bring some much-needed energy to the side following a couple of flat attacking displays.
Viktor Skripnik (Bremen head coach, r.): "They'll try to seize the initiative, but we'll have a plan of our own and they'll respect us."
Roger Schmidt (Bayer 04 head coach): "Wednesday's win did us good and obviously we want to end the week with another three points if we can."
Bremen have made a flying start to 2015, building on their pre-winter break success against Borussia Dortmund with back-to-back wins over Hertha Berlin and TSG 1899 Hoffenheim. Leverkusen are also unbeaten since the turn of the year after drawing with BVB and winning in the capital.
The Green-Whites' 1-0 victory in last season's corresponding fixture put an end to a five-game winless run against Leverkusen at the Weser Stadion, although Bayer 04 have won just twice on Bremen soil in the last ten years. The two sides played out a thrilling 3-3 draw earlier in the campaign.
Bremen: Wolf - Gebre Selassie, Galvez, Vestergaard, Garcia - Bargfrede - Fritz, Junuzovic - Bartels - Selke, di Santo
Leverkusen: Leno - Hilbert, Toprak, Spahic, Wendell - L. Bender, Castro - Bellarabi, Calhanoglu, Son - Kießling