It will be the first meeting between the two sides since March 2007, when current Liverpool manager Jurgen Klopp presided over a 1-0 victory for his Mainz side.
After impressively taking four points from their opening two games, it has been an extremely difficult period for Bundesliga new boys Arminia, losing seven matches in a row to fall into the automatic relegation places for the first time this season.
Uwe Neuhaus's side have been unfortunate in the most recent defeats to Bayer Leverkusen and RB Leipzig, though, with even Julian Nagelsmann admitting that his Leipzig side did not deserve the three points in their 2-1 victory last weekend.
After Angelino remarkably notched his sixth goal of the season in a tight first half, Arminia were their own worst victims once again as they over-zealously played out from the back, with Amos Pieper's dreadful back-pass intercepted by Dani Olmo. The Spanish midfielder laid the ball on a plate for Christopher Nkunku to double the hosts' lead, before Pieper was at fault once more by bringing down Alexander Sorloth in the penalty area.
However, the Norway striker missed his penalty, with legendary striker Fabian Klos finally scoring his first ever Bundesliga goal to give his side a fighting chance of nicking a point. Substitute Joakim Nilsson could have done exactly that, but his stretching effort from close range sailed over the bar as Arminia succumbed to yet another defeat.
Should Arminia perform as they have done in their last two matches against superior opposition than Mainz, though, they will have every chance of picking up a point or three for the first time since late September.
It could be a case of right team, wrong time for Arminia, however, with Mainz's form significantly picking up in recent weeks.
After losing their first six matches of the season, Jan-Moritz Lichte has guided his side to five points from three matches, with the rise in standards summed up by his disappointment in only picking up one point in the 1-1 draw with Hoffenheim last weekend.
Robert Quaison, who shined last season with 13 league goals, scored his first goal since matchday two after superb hold-up play by the in-form Jean-Philippe Mateta in the first half. The striker's clever back-heel found the onrushing Jean-Paul Boetius, who squared for his teammate to convert from close range.
Several excellent saves by goalkeeper Robin Zentner, plus a last-ditch block by Alexander Hack, kept the hosts ahead before Ryan Sessegnon - on loan from Tottenham Hotspur - superbly crossed for Ihlas Bebou to level proceedings. Hoffenheim survived despite Dennis Geiger's late red card for a cynical foul from behind, with Mateta surprisingly striking the post when one-on-one with Oliver Baumann.
There has certainly been plenty to build on in recent weeks for Mainz, meaning that they will head to Bielefeld fully believing that they can earn a second win of the season and potentially move four points clear of the automatic relegation places in the process.
Arminia Bielefeld Bundesliga form: LLLLLL
Mainz 05 Bundesliga form: LLLDWD
Neuhaus will be without Pieper after the central defender's second half against Leipzig became even worse by being substituted with a muscle injury, with Nilsson likely to replace him in the starting XI.
Otherwise the 61-year-old appears to have no other injury or suspension concerns. He will certainly be hoping Klos can kick on and get himself on the scoresheet more regularly now that the 32-year-old has finally broken his duck at the top level.
The 40-year-old has moved to a back three system in recent weeks with good success, so is unlikely to change tactics or personnel too much.
However, with Oztunali out, Lichte may be tempted into moving Boetius to right wing-back, with Quaison and Karim Onisiwo supporting Mateta.
Arminia Bielefeld possible starting lineup:
Ortega; Brunner, Nilsson, Van der Hoorn, Lucoqui; Seufert, Prietl; Doan, Hartel, Yabo; Klos
Mainz 05 possible starting lineup:
Zentner; St Juste, Hack, Niakhate; Boetius, Barreiro, Fernandes, Brosinski; Quaison, Onisiwo; Mateta
We say: Arminia Bielefeld 1-2 Mainz 05
We expect a closely fought affair in Bielefeld, with the visitors perhaps having a little too much firepower for their struggling opposition to handle.
Indeed, with Quaison looking back to his best last week and Mateta scoring seven goals in nine league games this season, Arminia must ensure they do not gift their opposition chances as regularly as they have been of late.