The Czech-born coach returned to the helm on March 9 having been sacked in late December following a poor run of form.
However, his replacement Gianfranco Zola failed to turn things around and Cagliari turned to Zeman again in their fight to stay up.
A draw against Empoli in his first game back gave many hope, but four successive defeats have followed and they sit nine points from safety with seven games remaining.
Sunday's 3-0 loss to Napoli was the final straw for Zeman, leaving Cagliari searching for a replacement ahead of their trip to Fiorentina this weekend.
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