The Belgian outfit have 16 points from their opening seven top-flight fixtures, while Leverkusen have already posted four defeats at the start of their Bundesliga campaign.
Match preview
Having finished in third position in the Bundesliga last season, much was expected of Leverkusen after they were able to retain the majority of their first-team squad over the summer.
However, a shock 4-3 defeat at the hands of Elversberg set Gerardo Seoane's side in the wrong direction, and they have failed to recover from that early DFB-Pokal exit.
While there was no shame in losing 1-0 at Borussia Dortmund on the opening day of the Bundesliga campaign, defeats to Augsburg, Hoffenheim and Freiburg were not expected.
A three-goal blitz at Mainz 05 at least got Leverkusen on the board in the Bundesliga, but they are currently down in 14th position in the standings.
In total, Seoane has witnessed his team concede 13 times in six matches, and things must improve defensively if they are going to challenge for qualification from a group which also features Atletico Madrid and Porto.
The biggest success of Brugge's summer has been retaining the services of Hans Vanaken, who had been heavily linked with a transfer to West Ham United.
As it stands, it remains unclear how the long-serving midfielder will react to that disappointment, but he is likely to be motivated to earn a move to a higher-profile club in the future.
Brugge have put together their best period of the season in recent weeks, posting four successive wins to move into third spot in the Jupiler League table.
Twelve goals were scored during that quartet of matches with Ferran Jutgla taking his tally to five strikes and three assists from seven outings this campaign.
These two teams have only ever met in one competitive match in Europe, that fixture coming in the 2006-07 UEFA Cup when they played out a 1-1 draw in Belgium.
Club Brugge form (all competitions):
Bayer Leverkusen form (all competitions):
Team News
Brugge will be without Clinton Mata after he picked up an injury in the derby triumph over Cercle Bruges on Friday night.
Raphael Onyedika could be drafted into midfield for his debut, with Denis Odoi dropping into the back three.
Key playmaker Noa Lang is not expected to recover from injury in time to feature in this fixture.
Despite making an impact from the substitutes' bench at the weekend, Chelsea loanee Callum Hudson-Odoi will likely remain among the Leverkusen replacements.
Charles Aranguiz will be considered for a recall in midfield, but Seoane may be prepared to stick with much of the side which started the defeat to Freiburg.
Club Brugge possible starting lineup:
Mignolet; Odoi, Mechele, Sylla; Olsen, Nielsen, Onyedika, Vanaken, Meijer; Sowah, Jutgla
Bayer Leverkusen possible starting lineup:
Hradecky; Kossounou, Tah, Tapsoba; Frimpong, Palacios, Andrich, Demirbay, Sinkgraven; Diaby, Schick
We say: Club Brugge 1-2 Bayer Leverkusen
There is an argument that Brugge are the favourites heading into this contest, particularly with home advantage in their favour. However, things must click into gear for Leverkusen at some stage, and we feel that they will do just enough to earn all three points on Wednesday.