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Mediterranean mussels ( Mytilus galloprovincialis) and blue mussels ( Mytilus edulis) are among the most consumed fishery products, but they are frequent vehicles of foodborne infection worldwide. In this study, we investigated the occurrence and seasonality of zoonotic protozoans in mussels farmed or sold at retail outlets in Italy. We collected and tested 1,440 M. galloprovincialis and 180 M. edulis. Pooled samples were molecularly tested for Giardia duodenalis, Cryptosporidium spp., and Toxoplasma gondii and then sequenced. Sixty-two (45.9%; 95% confidence interval, 37.5 to 54.3%) mussel pools tested positive for one or more of the investigated pathogens. Both Mytilus species and samples from all the investigated areas harbored pathogens. Mussels were statistically more contaminated by Cryptosporidium spp., followed by T. gondii and G. duodenalis assemblage A, and M. galloprovincialis was more contaminated than M. edulis ( P < 0.01). Contamination was more likely in mussels at retail outlets ( P < 0.05) than in those from farms and in mussels collected in spring ( P < 0.01) than in other seasons. This is the first report of T. gondii found in M. galloprovincialis in Italy and in M. edulis in Europe. The detection of zoonotic protozoans in a widely consumed food source indicates the need for a more detailed microbiological risk analysis, especially considering that bivalve mollusks are often consumed raw worldwide.