Pyrogallol promotes free radicals leading to oxidative stress and toxicity. There are however a lack of studies on oxidative stress and the antioxidant system of fish following exposure to pyrogallol. This study measured oxidative stress markers, antioxidant responses, and histological changes in catfish exposed to pyrogallol. Fish were divided into one of four experimental groups: control only, or 1, 5 or 10 mg/L pyrogallol. After 15 days, glutathione-S-transferase in the serum was decreased in fish exposed to either 5 or 10 mg/L pyrogallol relative to controls while superoxide dismutase and total antioxidant capacity were decreased significantly in fish exposed to 1, 5, or 10 mg/L pyrogallol. Conversely, catalase was increased in serum of fish exposed to 1, 5, or 10 mg/L pyrogallol compared to controls. The liver of fish treated with 1, 5, or 10 mg/L pyrogallol had significantly higher levels of oxidative stress markers (malondialdehyde, lipid peroxidation, hydroperoxide content, oxidised protein content, and DNA fragmentation %) that varied with concentration. Catfish exposed to either 1, 5, or 10 mg/L pyrogallol presented with notable histological alterations in the intestine, kidney, and muscles with prominent fibrosis, as intense deposition of collagen fibre was observed by Masson's trichrome staining. Overall, endpoints related to oxidative stress and antioxidant defence enzymes in fish may be early biomarkers of pyrogallol exposure and contamination in aquatic ecosystems. Additional studies should characterize oxidative stress indicators for their utility as biomarkers of effect.