Leverkusen have a four-point advantage over Schalke with six games of the season to go while the Royal Blues are currently three points ahead of fifth-place Freiburg.
Finishing third means an automatic berth in the group stage while fourth would involve a two-legged play-off tie towards the end of August.
That also means a return to pre-season training a fortnight earlier and a shortened summer holiday.
"They are certainly going to want to use this chance to breathe right down our necks," said Leverkusen midfielder Lars Bender on his club's website.
He could not have formulated that any better, according to Schalke goalkeeper Timo Hildebrand.
"We've got to be hungry against Leverkusen and reduce the deficit on our direct rivals to a point," he said.
"We want to get into the Champions League again. Games on a European stage are very special and we have got to give everything for this goal."
Hildebrand is optimistic about the Royal Blues' chances of overtaking Leverkusen between now and the end of the season, predicting that they could yet have a dip in form.
"We've already had our weak phase, but maybe they have one now," he said on his club's website.
"They have had a few problems lately. We are on a good run, but our performances have nevertheless fluctuated."
Hildebrand can be sure of his place in goal on Saturday while the rest of the team "picks itself", according to coach Jens Keller.
"We have such injury misfortune right now, but the lads who will play are highly motivated and have a lot of quality," he said.
Roman Neustadter is suspended while Jermaine ones is doubtful due to injury. Jefferson Farfan has been ruled out also, joining the likes of Tranquillo Barnetta, Chinedu Obasi, Kyriakos Papadopoulos, Klaas-Jan Huntelaar, Ibrahim Afellay and Lars Unerstall on the sidelines.