The present study evaluated the effect of chronic exposure to oxyfluorfen (OXY) on different physiological responses of male African catfish, Clarias gariepinus, and the ameliorative effect of Chlorella vulgaris. The fish (160 ± 5.10 g) were exposed to 1/20 LC50 of OXY (0.58 mg/L) for 60 consecutive days with or without co-administration of C. vulgaris (25 g/kg diet) in triplicate groups. The results revealed that chronic exposure to a sublethal level of OXY induced severe anemia and leukopenia. OXY-exposed fish experienced hypoproteinemia, marked lower AchE levels, and a significant increase in glucose, liver, and kidney function biomarkers. The DNA fragmentation of the liver increased by 15 % in fish compared to the control. On the other hand, lipid peroxidation, superoxide dismutase, and catalase activities were markedly increased in the liver and testes homogenates of the OXY-exposed fish. Meanwhile, total antioxidant capacity and glutathione S-transferase levels declined in the same tissues. Exposure to OXY induced a significant reduction in testosterone and luteinizing hormone levels and a significant increase in follicle stimulating hormone and estradiol. Meanwhile, C. vulgaris dietary supplementation succeeded in alleviating the negative impact of OXY on hematobiochemical parameters and restoring the antioxidant balance in the liver and testes. Furthermore, it ameliorated endocrine disruption and repaired sex hormone levels. In conclusion, exposure to OXY could induce systemic stress, oxidative stress, and endocrine disruption in male C. gariepinus. The dietary supplementation of C. vulgaris could be a potential protective strategy against the toxicity of OXY.