Ichthyophthirius multifiliis is a widespread, ciliated protozoan ectoparasite of fish. In the present study, we investigated the effects of metal nanoparticles on the reproduction and infectivity of free-living stages of I. multifiliis. We determined that ~50% of theronts could be killed within 30 min of exposure to either 20 ng mL−1 gold, 10 ng mL−1 silver or 5 ng mL−1 zinc oxide nanoparticles. Silver and zinc oxide nanoparticles at concentration of 10 and 5 ng mL−1 killed 100 and 97% of theronts, respectively and inhibited reproduction of tomonts after 2 h exposure. Gold nanoparticles at 20 ng mL killed 80 and 78% of tomonts and theronts 2 h post exposure, respectively. In vivo exposure studies using rainbow trout (Oncoryhnchus mykiss) demonstrated that theronts, which survived zinc oxide nanoparticles exposure, showed reduced infectivity compared with control theronts. No mortalities were recorded in the fish groups cohabited with theronts exposed to either nanoparticles compared with 100% mortality in the control group. On the basis of the results obtained from this study, metal nanoparticles particularly silver nanoparticles hold the best promise for the development of effective antiprotozoal agents useful in the management of ichthyophthiriosis in aquaculture.