The Bundesliga outfit are on a run of one win in 13 matches in the league, although that victory was a thumping 5-0 triumph over Paderborn.
That sequence has seen Mainz slip to 14th in the top flight, one point clear of the relegation zone, and a 4-2 defeat at fellow strugglers Borussia Dortmund on Friday turned out to be the final straw.
Under-23 coach Martin Schmidt has stepped into the void left by Dane Hjulmand and will take training on Tuesday.
Mainz finished seventh under Thomas Tuchel last season, but struggled to replicate that form following the arrival of Hjulmand from Nordsjaelland in May.
Mainz next face Eintracht Frankfurt on Saturday.
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