The hosts head into the weekend one position and two points ahead of Hertha, who will slip into the bottom three if Arminia Bielefeld avoid defeat against Augsburg on Saturday.
After losing their first six matches of the season and languishing on six points after their opening 13 matches, Mainz looked destined for the drop alongside faltering Schalke 04.
However, Die Nullfunfer have gone from strength to strength since appointing Bo Svensson as manager in early January, with the man who spent seven years at the club as a player between 2007 and 2014 taking 22 points from his 15 matches in charge so far.
Last weekend's entertaining 3-2 win against FC Koln was a particularly important one, as defeat would have meant ending the weekend in an automatic relegation position, with Koln leapfrogging out of the bottom three at their expense.
Svensson's side started on the front foot, with Jean-Paul Boetius firing them into an early lead after his effort from distance crashed off the underside of the bar and over the line.
Ondrej Duda maintained his 100% record from the penalty spot to level proceedings after Phillipp Mwene was adjudged to have handled the ball, before Ellyes Skhiri turned the game on its head by heading home at the back post from Jonas Hector's free kick.
Mainz had the last laugh, though, with Boetius turning provider with a pinpoint ball across Koln's penalty area for Karim Onisiwo to tap home, before Leandro Barreiro's superb first-time strike found the bottom corner to snatch a dramatic victory.
Victory against Hertha on Sunday would see Svensson's side move five points clear of the relegation zone with only five games remaining, surely signalling a masterstroke from their recently-appointed boss and a 13th successive season in Germany's top flight.
Hertha, meanwhile, have struggled to receive quite the same new manager bounce since re-appointing Pal Dardai to take over the club for a second time in February, although there have certainly been green shoots of recovery.
The 44-year-old faced the top five sides in the division in his first seven matches, losing to each of them while only scoring one goal.
However, Hertha have avoided defeat in Dardai's other five matches in charge so far, but he would have been frustrated only to pick up a point in a 2-2 draw against Borussia Monchengladbach at home last time out.
Indeed, Die Fohlen saw their goalkeeper Yann Sommer sent off after only 13 minutes for a trip on Jhon Cordoba when the Hertha forward was baring down on goal, with the hosts looking perfectly set up for a huge win after Santiago Ascacibar scored his first goal of the season with a fine strike from outside of the area.
Lars Stindl dispatched in confident fashion to leave Hertha staring a disastrous defeat in the face.
Dardai was clearly enraged with his side's performance, making three half-time substitutions, with Cordoba providing the response which his manager was looking for by levelling the proceedings four minutes after the break.
Matteo Guendouzi went close to finding a winner with a powerful effort from range, but Gladbach held on against the odds to leave Hertha only outside of the relegation zone on goal difference prior to Sunday's trip to Mainz.
The Hungary international will likely be Burkhardt's replacement against Hertha should he be ruled out as expected.
Otherwise, Svensson may select the same XI which recorded a vital victory against Koln, with the likes of Robin Quaison, Danny Latza and Robert Glatzel all capable of making an impact from the bench if called upon.
Mainz 05 possible starting lineup:
Zentner; St Juste, Bell, Niakhate; Da Costa, Barreiro, Kohr, Mwene; Szalai, Boetius; Onisiwo
Hertha Berlin possible starting lineup:
Schwolow; Klunter, Stark, Alderete; Zeefuik, Ascacibar, Guendouzi, Mittelstadt; Lukebakio, Cunha, Cordoba
We say: Mainz 05 2-1 Hertha Berlin
Mainz have serious momentum at the moment and we can envisage them narrowly edging Hertha to move away from the relegation zone.
Hertha certainly have the forward players to hurt Mainz in transition, though, so it would be no surprise to see a high-scoring affair which really could go either way.
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