Human viruses are widespread as contaminants in surface waters and represent a significant health risk. Viral pathogens can persist in aquatic ecosystems and cause infections via contaminated water or food. Among the different factors governing the environmental persistence of enteric viruses, removal by indigenous microorganisms, in particular predation by protists, has received little attention to date. This study aims to determine the contribution of indigenous protists to the inactivation of human viruses in different surface waters. Incubation of human echovirus 11 (E11) in water from Lake Geneva and seawater led to an inactivation of 2.5-log within 48 hours at 22°C, whereas inactivation in sterile controls was minor (0.8-log reduction). This inactivation was mainly attributed to the action of protists in the eukaryotic fraction of the samples. The inactivation of viruses was shown to be temperature-dependent, with a complete inhibition of biological inactivation at 8°C. In addition, inactivation depended on both the species of virus and protist species. Among three protist isolates tested (Paraphysomonas sp., Uronema marinum and Caecitellus paraparvulus), Caecitellus paraparvuluswas particularly efficient at removing E11 (2.1-log reduction over four days with an initial protists concentration of 1000 cells / ml). In conclusion, this study suggests that indigenous protists present in lakes and oceans are important biological contributors to the inactivation of E11. These results pave the way for further research to better understand how protists control human viral pathogens in aquatic ecosystems and how microbial inactivation could be exploited as a water treatment solution to enhance microbial safety.