Background: Technology advancement in the agricultural production which prompted the use of herbicides to control weeds is found to be potentially harmful to the environment and human health. Method:  lethal and sub-lethal effect of glyphosate on some biochemical parameters and growth responses of African catfish, Clarias gariepinus were investigated using static renewal bioassays and continuous aeration for a period of 96 h and 28 days using varying concentrations (20.0 mg/l, 30.0 mg/l, 40.0 mg/l, 50.0 mg/l and 60.0 mg/l) and (1.0 mg/l, 2.0mg/l, 3.0mg/l, 4.0mg/l and 5.0mg/l) respectively.  At the end of the experiments, the fish were sacrificed and the blood samples were collected. The gill and liver of the fish were removed for biochemical bioassay. Result: During the exposure period, the fish showed different abnormal behaviours such as restlessness, loss of balance, respiratory distress, grouping together, darting movements, and loss of equilibrium, mucous secretion and erratic swimming. Compared with the control, the result showed a significant increase (P < 0.05) in the activities of alanine aminotransferase (ALT), and aspartate aminotransferase (AST), superoxide dismutase (SOD) and lactate dehydrogenase (LDH) in the gill, liver and blood of Clarias gariepinus exposed to glyphosate for 96 h while the activities of enzymes ALT, and AST in both the blood and the gill of fish exposed to glyphosate for 28 dsys, except in liver where it showed a significant reduction. However the values of SOD and LDH showed significant increase in the blood with a noticeable decrease in both the gill and liver of fish. Growth rate was insignificantly different (p˃0.05) as the concentration increased compared to the control experiment. The highest percentage weight gain (12%) was observed in the control, while the lowest percentage weight gain (7%) was observed in the highest concentration. The specific growth rate of the fish reduced (p˃0.05) insignificantly as the concentration increased. Conclusion: The study showed that sub-lethal concentrations of glyphosate are harmful to Clarias gariepinus. The implication of these results in rational exploitation and conservation of fishery resources and the public health risk of consuming glyphosate-exposed fish are highlighted.