Defeats for either side last weekend left Mainz above last-placed Darmstadt only on goal difference, with Union dangling just six points above them.
Match preview
Without a win in nine games, Mainz last tasted victory against RB Leipzig in November, when Jan Siewert took charge of his first match as head coach of Die Nullfunfer.
Following back-to-back 1-0 defeats - to Eintracht Frankfurt, then at home to Werder Bremen - the club's 15-year stay in Germany's top flight is in serious jeopardy, as they currently occupy 17th place in the Bundesliga standings.
Six points adrift of safety and four shy of the promotion/demotion playoff place, Mainz fans must be fearing the worst - particularly as they have witnessed first-hand their team's shortcomings on many occasions.
Having picked up only five points on home soil this season, FSV have also scored the fewest home goals (six), so they will be desperate to improve that dismal record in Wednesday's game-in-hand on several sides above them.
Now playing a fixture initially called off due to icy conditions at MEWA Arena last month, Siewert's side will also seek revenge for a 4-1 defeat in August's reverse fixture, which set the tone for a tough season ahead.
Not only have Union Berlin lost just one of their last 10 competitive matches against Mainz, the capital club have also come out on top in four of the teams' last five league meetings.
Given their hosts' ongoing woes, Die Eisernen may fancy doing the double over them this season - particularly as new coach Nenad Bjelica seems to have steadied the ship since being appointed in late November.
Since the departure of much-loved boss Urs Fischer, who led them into the Champions League before finally running out of steam, Union have lost only two Bundesliga matches, after failing to take a single point from the previous nine.
Bjelica's men edged out Darmstadt in a crucial six-pointer at the end of January, but were then beaten by Leipzig in their first February fixture and remain in some danger, sitting just one place above the relegation playoff spot now occupied by Koln.
Since reaching the Bundesliga for the first time in 2019, Union had never before put fewer than 20 points on the board at this stage of the season, but with only a league-low four earned on the road, that should perhaps come as no surprise.
Mainz 05 Bundesliga form:
D
L
D
D
L
L
Mainz 05 form (all competitions):
L
D
W
D
L
L
Union Berlin Bundesliga form:
L
W
D
L
W
L
Team News
Jan Siewert will again be without Lee Jae-sung in midweek, as the winger is still away with South Korea at the Asian Cup; in addition, Brajan Gruda and Germany Under-21 striker Nelson Weiper are set to be sidelined by injury.
Stefan Bell will be absent for a few weeks yet, as the central defender has been stricken by a serious bacterial infection.
Mainz recently strengthened their squad by signing Nadiem Amiri, who joined from league leaders Bayer Leverkusen for an undisclosed fee, and after making his debut at the weekend he should start again on Wednesday.
Meanwhile, Union cannot count on Josip Juranovic, but Frederik Ronnow, Alex Kral and Diogo Leite may be back in the visitors' squad after illness.
Captain Christopher Trimmel was sent off last time out and must serve a suspension, so USA winger Brenden Aaronson should fill in on the right flank.
After arriving from PSV during the winter transfer window, Yorbe Vertessen partnered Benedict Hollerbach up front against Leipzig, but Kevin Volland could now come back into the starting XI.
Mainz 05 possible starting lineup:
Zentner; Widmer, Van den Berg, Caci, Mwene; Krauss, Barreiro; Burkardt, Amiri, Onisiwo; Ajorque
Union Berlin possible starting lineup:
Schwolow; Knoche, Vogt, Doekhi; Khedira; Aaronson, Schafer, Tousart, Gosens; Volland, Hollerbach