BVB came out 4-2 winners in the first leg a fortnight ago and seem well on their way to the quarterfinals, but will be eager to put on a strong performance in front of their home fans in the second leg.
Jurgen Klopp will be without long-term casualties Ilkay Gundogan, Neven Subotic and Sven Bender, but none of his players are suspended. He will also welcome Mats Hummels, who missed the first leg, back into his starting XI.
Here is Klopp's most likely IX in full:
Goalkeeper: Roman Weidenfeller
Vice-captain Roman Weidenfeller will play between the posts on Wednesday. Like many others in Klopp's team, he is the only fit, established first-team player in his position and thus his inclusion in the first team can be considered a given.
Right-Back: Lukasz Piszczek
Right-back Lukasz Piszczek left the pitch with an apparent muscular injury on Saturday, prompting concerns from BVB fans. But the Poland international returned to training on Monday and it appears that he will be fit and ready to take on Zenit.
Centre-Back: Sokratis Papastathopoulos
The rare constant in Dortmund's defense this season, Sokratis Papastathopoulos, will start at center-back in place of Subotic. He's had time to reform a partnership with Mats Hummels, who will replace Manuel Friedrich in Klopp's XI.
Centre-Back: Mats Hummels
Mats Hummels missed the first leg of the Zenit clash due to an injury, but he has since returned to action and led to a general improvement in the BVB defense. Prior to last weekend's loss to Gladbach, BVB kept back-to-back clean sheets in the matches that came after Hummels' return to action. The 25-year-old has only participated in three Champions League fixtures this season and will look to impress on the big stage once more.
Left-Back: Marcel Schmelzer
Marcel Schmelzer has played every minute of every Dortmund game in 2014 and will surely start again on Wednesday. The Germany international at present seems to be the only left-back Klopp trusts, with Erik Durm and Jeremy Dudziak apparently not yet up to par.
Defensive Midfield: Sebastian Kehl
With Bender injured, Sebastian Kehl will deputize in defensive midfield. The veteran has a different style of play from the extremely energetic and industrious Bender, but even in his advanced years he remains a reliable substitute.
Defensive Midfield: Nuri Sahin
Nuri Sahin will start in a holding role alongside Kehl on Wednesday, the Turkey international replacing the injured Gundogan in Klopp's starting lineup. Sahin has saved his best performances for the Champions League this season and will hope to carry his fine form through the second leg of the round of 16.
Right Wing: Pierre-Emerick Aubameyang
Pierre-Emerick Aubameyang has consistently found the target in the Bundesliga, but the Gabon international is yet to make his impression in the Champions league. His only goal on the continental stage this season came against Napoli in November. Still, in the absence of Jakub Blaszczykowski, Aubameyang is a lock for a starting role on the right wing.
Centre-Attacking Midfield: Henrikh Mkhitaryan
Henrikh Mkhitaryan missed last weekend's loss to Monchengladbach due to suspension for accumulated cautions. Given the result of that match and Jonas Hofmann's underwhelming performance as the Armenia international's stand-in, there's little doubt that Mkhitaryan will start against Zenit.
Left Wing: Marco Reus
Marco Reus missed Dortmund's last two matches due to a muscular strain, but was in training on Monday and is likely to return to action for the Zenit match. The Germany international scored and gave two assists in the first leg, and BVB will look to him to provide a spark of inspiration on Wednesday.
Centre-Forward: Robert Lewandowski
Robert Lewandowski scored twice in the first leg and will be keen to put at least one or two more goals into the Zenit net. The Poland international returned from a cruciate ligament strain last weekend and is fit to play, although he will have to be careful to avoid a booking that would see him suspended in the event that BVB progress to the quarterfinals.