This study aimed to evaluate the hematological profile and relative condition factor of naturally parasitized Nile tilapia from 12 fish farms in southern Brazil. A total of 240 fish were collected from four regions of the state of Santa Catarina. They were anesthetized, and the blood was collected by puncturing the caudal vein. Subsequently, the fish were necropsied for parasitological analysis. The results were compared with the Kruskal-Wallis test, and the correlations were verified with the Spearman test (P < 0.05). The parasitological analysis revealed high infestations by Ichthyophthirius multifiliis on the fish gills of the south and west regions. The presence of Trichodina magna and Trichodina compacta was observed in low intensity on the body surface of fish from all facilities. Trichodina spp. was found in high intensity parasitizing the fish gills of northern, Itajaí valley and western regions, nonetheless, in those regions, the presence of Monogenea, Cichlidogyrus sclerosus, and Cichlidogyrus halli, on fish gills was observed. The hematological profile presented altered parameters, featuring monocytosis and thrombocytopenia, possibly associated with high parasitic intensities. The observed correlations suggest that neutrophils and monocytes are directly involved in an organic defense against parasites. Monocytes are mainly targeted in the defense against I. multifiliis.