Plant-based ingredients are successfully replacing fishmeal in fish feeds. However, this practice increases the risk of feed contamination by mycotoxins that reduce production and heath associated with oxidative damage. The aim of this study was to determine whether feed contaminated with environmentally relevant concentrations of ochratoxin A (OTA) causes muscle oxidative damage in tambaqui (Colossoma macropomum), and to determine whether this feed impairs fatty acid profiles in fish meat. Final mean weight, weight gain, daily weight gain, feed efficiency, and specific growth rate were significantly lower in fish fed 1.6 and 2.4 mg OTA/kg compared to those fed basal diet, while feed conversion was significantly higher in these same groups compared to the basal group. Levels of reactive oxygen species and lipid peroxidation in muscle were significantly higher in fish fed 1.6 and 2.4 mg OTA/kg compared to those in the basal group. Likewise, muscle superoxide dismutase and glutathione peroxidase activities were significantly higher in fish fed 1.6 and 2.4 mg OTA/kg then in those fed basal feed. The total content of saturated fatty acids was significantly higher, and total content of polyunsaturated fatty acids was significantly lower in fish fed 2.4 mg OTA/kg compared to those fed basal feed. Taken together, the data suggest that OTA-contaminated feed induces oxidative damage and disturbs enzymatic and non-enzymatic antioxidant responses in tambaqui meat. The perturbations of fatty acid profiles in fish meat appears to mediated by oxidative damage, representing negative impact on fish health and presenting concerns for consumers of fish.