The identification of the molecular mechanisms by which parasites and hosts interact with each other is crucial in understanding how parasites evade the host’s immune system and ultimately cause disease. Through immunoaffinity in association with high-throughput proteomic analysis, we defined the repertoire of antigenic targets involved in the antibody response to H. meleagridis. As such, we isolated immunogenic proteins of the protozoan by immunoprecipitation employing sera from chickens and turkeys, vaccinated and challenged, with an attenuated and virulent strain of H. meleagridis, respectively. Amongst all analyzed samples, a total of 111 proteins were identified as putative immunogenic proteins. Separating the data amongst the two hosts studied, 88 proteins were identified with chicken immune sera, and 67 with turkey sera. From the antigenic proteins identified with chicken immune sera, 54 were classified as proteins displaying putative antigenicity and 46 whilst using turkey immune sera.