Trypanosoma danilewskyi is a protozoan that lives in blood and other tissues of fish. In the aquaculture industry, economic losses may be substantial, since the prevalence of infection may approach 100% and the parasite may cause significant mortality in farmed carp. Most of the surviving fish acquire resistance after elimination of the primary infection. In this study, we examined whether protection against infection could be induced in naïve goldfish immunized with excretory-secretory (ES) products of the parasite. The ES extracts were administered in conjunction with Freund's complete or incomplete adjuvant (FCA and FIA, respectively). Parameters used to assess the efficacy of immunization after challenge infection, included prevalence of infection, abundance of parasites, and presence of parasite-specific antibodies. Intraperitoneal inoculation of ES products in FCA conferred protection against T. danilewskyi infection (P<0.05). Administration of ES products (with or without FIA) conferred insignificant levels of protection. In an attempt to identify the immunogenic ES molecules, we assessed whether anti-parasite antibodies present in the serum collected from experimentally infected fish or rabbits immunized with ES recognized parasite ES antigens. An immunoblot using rabbit anti-parasite antibody revealed a recognition profile of molecules (two antigens of approximately 102-104 and 70-72kDa) similar to that of immune goldfish serum. While the antigens that confer protection need further molecular characterization, our results suggest that the administration of ES products may allow for the design of control strategies for T. danilewskyi.