Both teams have endured a tough campaign and will enter the match desperate for points, with only eight games remaining between now and the season finale.
Back in the German top-flight after 11 years, Bielefeld look set to go down to 2. Bundesliga again.
Languishing second from bottom in the league standings with just 22 points from 26 games, the Blues have won only six games all season.
An important reason for their struggles has been a toothless attack, managing only 20 goals thus far, the lowest in the division after Schalke (16).
Japanese star Ritsu Doan is their most prolific scorer with four league goals, followed by Fabian Klos, who's accrued another three.
Mainz 05 vs Arminia Bielefeld Head-To-Head
In 14 games between the sides, Bielefeld hold a better record with exactly half the number of victories from those clashes. They have lost to Mainz only four times.
In the first leg of their campaign this season, the promoted side eked out a 2-1 win at home.
Mainz 05 Form Guide (all competitions): L-D-W-W-D
Arminia Bielefeld Form Guide (all competitions): L-D-L-W-L
Mainz 05 vs Arminia Bielefeld Team News
Die Nullfünfer have been handed a huge boost with the return of Danny Da Costa, who was forced off with a hamstring injury against Hoffenheim last month.
Head coach Bo Svensson has a clean bill of health going into the match with all key players available for selection.
Amos Pieper has been suspended from the clash for an accumulation of cards.
But on the bright side, Ritsu Doan is expected to be fully fit after missing Japan's international fixtures with a concussion. Meanwhile, Jacob Laursen has also returned to full fitness.
Suspended: Amos Pieper
Mainz 05 vs Arminia Bielefeld Predicted XI
Mainz 05 (3-4-2-1): Robin Zentner; Jeremiah St. Juste, Stefan Bell, Moussa Niakhate; Danny Da Costa, Leandro Barreiro, Dominik Kohr, Phillip Mwene; Jean-Paul Boetius, Robin Quaison; Robert Glatzel.
Arminia Bielefeld (4-4-2): Stefan Ortega; Cedric Brunner, Mike van der Hoorn, Joakim Nilsson, Jacob Laursen; Masaya Okugawa, Manuel Prietl, Arne Maier, Michel Vlap; Ritsu Doan, Fabian Klos.
Mainz 05 vs Arminia Bielefeld Prediction
Despite their position, Mainz have improved lately, and should make it three wins in a row against the luckless Bielefeld.
Prediction: Mainz 05 2-1 Arminia Bielefeld