Aim: The current study was directed to investigate the immunotoxic and oxidative stress effects of Roundup and Stomp herbicides and their combination on Nile catfish (Clarias gariepinus). Materials and Methods: The experiment was carried out on 120 fish that randomly divided into four equal groups with three replicates: The first group kept as control, the second group exposed to 1/2 96 h lethal concentration 50 (LC50) of Roundup, the third group exposed to 1/2 96 h LC50 of Stomp, and the fourth one exposed to a combination of Roundup and Stomp at previously-mentioned doses. The experiment was terminated after 15 days; blood samples were obtained at 1st, 8th, and 15th days of treatment where the sera were separated for estimation of antioxidant enzymes. Meanwhile, at 15th day of exposure part of blood was collected from all groups with an anticoagulant for evaluation of phagocytic activity, then the fish were sacrificed, and specimens from the liver of all groups were obtained for histopathological examination. Results: Our results indicated that both herbicides either individually or in combination elucidated significant decrease in phagocytic activity that was highly marked in group exposed to both herbicides. Furthermore, our data elicited an obvious elevation in the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Meanwhile, the data depicted reduction in levels of reduced glutathione (GSH) and glutathione-S-transferase (GST). Histopathological investigation of liver proved the aforementioned results. Conclusion: It could be concluded that either Roundup or Stomp alone cause significant deleterious effects on aquatic vertebrates. However, the use of their combination enhanced their toxic effects. Toxicity can end up in humans through the food chain.