The home side also suffered a humbling defeat last time out, as Union were swept aside by local rivals Hertha Berlin 4-0 to slip further down the table.
For all the promise that Union have shown during their inaugural campaign in the Bundesliga, the capital side were no match for Hertha last Friday at the Olympiastadion.
Hertha subjected Union to their fourth defeat on the bounce in all competitions last time out, and Fischer's side have only won one of their last five fixtures in Germany's top flight.
Eintracht Frankfurt, who were the last side to suffer defeat against Union in February, are the only other team in the division currently on a three-game losing streak.
The Bundesliga new boys are in a strong position to avoid a swift return to the second division, however, although 16th-placed Fortuna Dusseldorf could move to within three points of Union with a victory over Schalke on Wednesday.
Nevertheless, Fischer will be encouraged by his side's home form as six of Union's nine victories this season have come in front of their own fans.
As far as Mainz are concerned, coming up against an in-form Leipzig side would be no easy feat for any team right now, but Julian Nagelsmann's men simply outclassed Mainz in their own territory.
Timo Werner's hat-trick subjected Mainz to their 16th Bundesliga defeat of the season - a result which leaves them in 15th on 27 points - three above the relegation playoff spot after 27 games.
The outlook will not fill the Mainz faithful with confidence heading into the business end of the season; basement side SC Paderborn are the only team with more defeats than Achim Beierlorzer's men, and Mainz have shipped 60 goals this term - more than any other side.
Nevertheless, Beierlorzer's side did manage to string together a three-game unbeaten streak before the defeat to Leipzig, and they have only lost twice in their last five league matches on the road.
However, owing to Union's superior goal difference, Mainz would have to record a victory by five goals in order to leapfrog their opponents in the table.
Union Berlin Bundesliga form: LWDLLL
Union Berlin form (all competitions): WDLLLL
Mainz 05 Bundesliga form: DLWDDL
As the Bundesliga fixture schedule becomes all the more demanding after a two-month suspension, both managers will be expected to tinker with their sides for the midweek clash.
With regards to Union, defender Keven Schlotterbeck is likely to return to the side after missing out the defeat to Hertha through suspension.
Union Berlin possible starting lineup:
Gikiewicz; Friedrich, Schlotterbeck, Subotic; Trimmel, Gentner, Andrich, Lenz; Malli, Bulter; Andersson
Mainz 05 possible starting lineup:
Muller; Baku, Niakhate, St. Juste, Brosinski; Boetius, Latza, Kunde, Oztunali; Quaison; Mateta
We say: Union Berlin 1-0 Mainz 05
Even though Union will be without the support of their loyal crowd for some time to come, Fischer's men have produced some impressive performances on home soil this season. As a result, we are struggling to see a Mainz side lacking in confidence coming away with anything on Wednesday evening.