Epitheliocystis is an emergent infectious disease affecting fish gills and skin worldwide. Few studies document their distribution in wild and cultured fish in Latin America. This study reports the epitheliocystis distribution and prevalence, histopathological index (HI), and its possible relation with other observed pathologies in the gills of cultured tilapias Oreochromis niloticus in ponds and cages of three states of southwestern Mexico. In Guerrero, the number of affected fishes was less (29.2%) compared to Oaxaca (39.8%) and Chiapas (49.1%), with significant difference (Gadj = 13.39, df = 2, P = 0.01). The size of the cysts was between 5.37 to 52.96 μm, and most of the analyzed fish showed a low number of cysts per gill arch. The prevalence by regions was varied (0 to 75%) and no correlation (r = -0.002, P = 0.659, n = 474) between epitheliocystis prevalence and type culture. The fish had a low infestation of Trichodina sp. and monogeneans plus different pathologies such as inflammation, eosinophilic cells, rodlet cells, telangiectasia, edema, and thrombosis. The correlation analyses show a low inverse correlation (r = -0.281, P = 0.000, n = 474) between epitheliocystis prevalence and fish weight; and a low correlation (r = 0.372, P = 0.000, n = 474) between epitheliocystis prevalence vs. HI. The presence of the pathologies registered in this study seems to be possibly associated with other conditions like water quality or toxicants. This research is the first scientific study documenting the presence and distribution of epitheliocystis in Mexico.