This fixture ended 1-1 in June last season, which would represent a decent result for Manuel Baum's side should Schalke manage to repeat it.
19-year-old Matthew Hoppe made his debut in attack for the visitors, with the young American firing wide in the early exchanges. However, Breel Embolo's strike rebounded into the path of Florian Neuhaus, whose scuffed effort somehow squeezed underneath five Schalke defenders and goalkeeper Fredrik Ronnow all desperately attempting to block it.
An upset potentially looked on the cards when Marcus Thuram carelessly gave the ball away to Mark Uth in his own half, with Schalke's most talented player deliciously scooping the ball through to Benito Ramen, who did not disappoint by firing into the far corner. However, as has so often proved the case this season, Schalke's hopes were short-lived after Neuhaus picked out Oscar Wendt's overlapping run, with the left-back placing the ball underneath the outrushing Ronnow.
Goals from Thuram and Hannes Wolf put any doubts regarding the result to bed in the second half, with Baum surely reverting to a back five against Leverkusen this weekend after such a disastrous defensive performance. His side will remain bottom of the table if they fail to win.
Having won eight of their previous nine matches in all competitions, Leverkusen were frustrated by Hertha Berlin in a 0-0 home draw last weekend.
Peter Bosz's side never found their usual attacking fluency against an unusually disciplined Hertha outfit, with their best chances in the game restricted to several Kerem Demirbay long shots. The midfielder has generally been a mainstay for Leverkusen in recent seasons, but the 27-year-old was actually making his first league start in six weeks, and perhaps found himself a little too eager to impress by having one too many speculative efforts from range.
Hertha almost snatched all three points with a Jessic Ngankam header in injury time, but a point for each side was fair in a tepid affair. Bosz's side were allowed to play with their usual attacking flair in the 3-2 win at Nice in the Europa League in midweek, wrapping up qualification to the knockout stages with a game to spare.
Should Bayern Munich avoid defeat at home to RB Leipzig on Saturday, Bosz's side will have the chance to move second in the table with victory at bottom-placed Schalke.
Schalke 04 Bundesliga form: DLDDLL
Schalke 04 form (all competitions): LDWDLL
Bayer Leverkusen Bundesliga form: WWWWWD
Bayer Leverkusen form (all competitions): WWWWDW
Baum moved to a back four in the absence of Sane at Gladbach, but is likely to tuck Malick Thiaw inside from left-back and revert to the back five system which had helped his side become tougher to beat in previous matches.
Nabil Bentaleb and Amine Harit have not featured since being involved in a training ground bust-up with assistant manager Naldo, and may sit out one more match as further punishment. Vedad Ibisevic will not play for the club again with his contract set to be terminated next month.
Charles Aranguiz and Sven Bender are also unlikely to make the trip to Schalke with muscular and ankle problems respectively, with Bosz's toughest decision whether to start Patrik Schick or Lucas Alario in attack should the latter shake off the minor injury which saw him sit out the scoreless draw with Hertha.
Edmond Tapsoba should return to the side having served his isolation period following his positive coronavirus test.
Schalke 04 possible starting lineup:
Ronnow; Thiaw, Kabak, Nastasic; Ludewig, Mascarell, Stambouli, Serdar, Raman; Uth, Hoppe
Bayer Leverkusen possible starting lineup:
Hradecky; Bender, Tah, Tapsoba, Sinkgraven; Wirtz, Baumgartlinger, Demirbay; Bailey, Alario, Diaby
We say: Schalke 04 0-2 Bayer Leverkusen
Both sides are likely to be missing several first-team players, but Leverkusen have greater squad depth to cope and as such we can envisage a comfortable victory for the visitors.