The visitors, meanwhile, have lost two successive league games and they will hope that run comes to an end in Gelsenkirchen.
Match preview
Schalke's 2-1 defeat away to Werder Bremen on Saturday evening was their eight consecutive loss in all competitions, with their last league points coming on September 10.
As such, it is little surprise that VfL Bochum - who were the team Schalke took three points against on that day - have moved above them in recent weeks, with new head coach Thomas Reis powerless to stop the rot in his first two games in charge.
However, the former Bochum boss would likely point to the fact that his new side have only conceded two goals in both of their defeats, compared to 17 across his predecessor Frank Kramer's final five matches in the managerial dugout.
With league leaders Bayern Munich arriving at Geltins-Arena in the final match prior to breaking for the World Cup, though, Reis will be feeling under significant pressure to claim a positive result against Mainz on Wednesday, otherwise Schalke's position will be looking perilous upon their return to action after Christmas.
Mainz, meanwhile, were beaten 3-0 at home to Wolfsburg on Saturday to fall into the bottom half of the table ahead of the domestic round of fixtures in midweek.
In truth, there was little to split the two sides on the day with the notable exception of their finishing capabilities, with the Wolves scoring from all three of their shots on target, compared to Mainz who converted none of their three.
Indeed, Bo Svensson's side enjoyed more shots, more possession and more corners throughout the course of the match, but they blanked in front of goal for the first time since August to fall to a second straight defeat having lost 6-2 to Bayern in their previous outing.
There is certainly no need to panic with a solid enough start to the season placing them directly in between the top four and the relegation zone - with a seven-point gap to both - but the 43-year-old will be urging his side to return to winning ways on Wednesday and pile the misery on struggling Schalke.
Schalke 04 Bundesliga form:
L
L
L
L
L
L
Schalke 04 form (all competitions):
L
L
L
L
L
L
Mainz 05 Bundesliga form:
L
D
W
W
L
L
Mainz 05 form (all competitions):
D
W
W
W
L
L
Team News
Schalke's injury list continues to be a lengthy one, with Marius Bulter, Ralf Fahrmann, Thomas Ouwejan, Leo Greiml, Rodrigo Zalazar, Sepp van den Berg, Ibrahima Cisse and Marcin Kaminski all unlikely to feature on Wednesday.
Reis could turn to the likes of Dominick Drexler, who scored a late consolation goal from the bench in Bremen last time out, and Sebastian Polter as he looks to find more offensive productivity.
Mainz, on the other hand, are only expected to be missing Maxim Leitsch and Marlon Mustapha for their trip to Gelsenkirchen in midweek.
Svensson generally makes very few alterations to his starting XI, but he may have been dissatisfied with his side's wastefulness during their defeat to Wolfsburg, with Jonathan Burkardt and Angelo Fulgini potentially handed chances on Wednesday.
Schalke 04 possible starting lineup:
Schwolow; Brunner, Yoshida, Matriciani, Mohr; Kral, Flick; Drexler, Polter, Bulter; Terodde
Mainz 05 possible starting lineup:
Zentner; Bell, Hack, Caci; Widmer, Barkok, Kohr, Caricol; Burkardt, Fulgini; Onisiwo
We say: Schalke 04 1-1 Mainz 05
With Schalke facing Bayern in their final match prior to the World Cup, their losing streak needs to come to an end on Wednesday if they are to avoid being even further stranded in the automatic relegation places.
Mainz have looked a little out of sorts in recent matches and we can see them having to settle for a share of the spoils against their struggling opponents.