The visitors, meanwhile, moved outside of the relegation places after stunning Union Berlin at the weekend.
Match preview
Koln's fourth match in 10 days ended in a 2-0 defeat away to Freiburg on Sunday, with Steffen Baumgart's side languishing in 12th position as a result.
Having been dumped out of the Europa Conference League after failing to beat Nice at home as was required in order to progress on Thursday, claiming a positive result away from home against one of the division's in-form teams always felt like being a tall order for Koln.
Both sides appeared to be tired from their European exertions during a quiet first half, but goals from Jeong Woo-yeong and Michael Gregoritsch either side of the hour mark took the game away from the visitors.
Baumgart will be hoping for a much better performance from his side at RheinEnergieStadion on Wednesday, when they will need to be on their game against an opponent likely to be full of confidence after registering a huge win at the weekend.
Indeed, very few people could have seen Leverkusen's 5-0 win against Union Berlin coming on Sunday, with the victory moving them out of the bottom three and denying their opponents a return to the top of the table in the process.
All five goals for Xabi Alonso's side came during a crazy 30-minute period after the half-time interval, with Moussa Diaby bagging a brace within the space of three minutes to leave the visitors stunned.
As a result, Leverkusen climbed one point above Hertha Berlin and Stuttgart in the table, although with those two teams playing each other on Tuesday, they are guaranteed to find themselves below one of them again before kicking-off in Cologne 24 hours later.
However, with a home match against Stuttgart to come in their final match before breaking for the World Cup, Alonso's side's destiny is back in their own hands in terms of ending this period outside of the bottom three, which would help them focus on moving even further up the table when they return to action after Christmas.
FC Koln Bundesliga form:
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D
L
FC Koln form (all competitions):
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L
Bayer Leverkusen Bundesliga form:
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Bayer Leverkusen form (all competitions):
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D
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W
Team News
Koln's fixture pile-up has not been helped by missing several players through injury, with Mark Uth, Florian Dietz, Jonas Hector, Dejan Ljubicic, Tim Lemperle, Dimitrios Limnios, Timo Hubers and Sebastian Andersson all unlikely to feature for them until after the World Cup.
The likes of Denis Huseinbasic, Sargis Adamyan and Jan Thielmann provide options to freshen things up having only appeared from the substitutes' bench during their side's defeat to Freiburg on Sunday.
Alonso, on the other hand, may not want to change a winning team, but he will be mindful of fatigue setting in before the World Cup begins later this month.
As such, Jonathan Tah, Callum Hudson-Odoi and Exequiel Palacios could earn recalls to the starting XI, but Charles Aranguiz, Sardar Azmoun and Florian Wirtz remain sidelined through injury.
FC Koln possible starting lineup:
Schwabe; Schmitz, Soldo, Kilian, Pedersen; Martel, Skhiri; Thielmann, Duda, Kainz; Tigges
Bayer Leverkusen possible starting lineup:
Hradecky; Tah, Tapsoba, Hincapie; Frimpong, Palacios, Andrich, Bakker; Diaby, Hudson-Odoi; Hlozek
We say: FC Koln 1-2 Bayer Leverkusen
We can envisage Leverkusen building on their huge win against Union Berlin at the weekend with another victory.
Koln look a little out of sorts at present having had their amount of matches compiled by numerous injuries, with the visitors undoubtedly possessing the attacking ability to punish them.