With Jan Kirchhoff out injured, Julian Baumgartlinger will most likely start in defensive midfield, with Eugen Polanski filling in alongside him on the right.
Nikita Rukavytsya and Nicolai Müller compete for the spot alongside Adám Szalai up front.
Otherwise, manager Tuchel could field an unchanged team.
Frankfurt are still fourth in the table and put in a strong performance last weekend, which earned them a draw at Schalke. It remains to be seen how they will deal with the absence of Anderson at centre-back.
Mainz are in solid form as well, despite two losses in a row at Hamburg and against Dortmund. If they take their chances more often, a result here would not be a big surprise.
Expect Frankfurt to try to dominate possession at home and Mainz to wait for their chances on the break.
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