The present study was undertaken to evaluate the effects of cadmium chloride and commercial formulation of glyphosate (Roundup®) on oxidative stress biomarkers in the Nile tilapia, Oreochromis niloticus through three exposure periods with different concentrations of LC50. The 96h-LC50 were determined for CdCl2 (132 mg/l), glyphosate (9.63 mg/l), CdCl2 in mixture (41.30 mg/l) and glyphosate in mixture (2.75 mg/l), respectively. The fish was exposed to these concentrations separately and mixed for 4 days as well as two sublethal concentrations (1/4 and 1/10 LC50) for 8 days and 45 days, respectively. Gills and liver cells of the exposed fish were taken after 4, 8 and 45 days to investigate the variation in activity of lipid peroxidation malonaldehyde (MDA) and antioxidant enzymes of catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST) and reduced glutathione (GSH). Where, in gills activity levels of SOD decreased after 4, 8 days in all treatments due to high concentration of pollutants but increased after 45 days in glyphosate and cadmium due to low oxidative stress and decreased in mixture. Also, in the liver activity of SOD decreased in glyphosate and cadmium and increased in mixture in periods 4, 8 days but, increased in 45 days in glyphosate and mixture and decreased in cadmium due to its toxicity. The activity of CAT decreased in gills and liver after 4 days but increased after 8, 45 days due to low concentration of contaminants. The activity of GST increased in gills and liver after 4, 8 days but decreased in liver after 45 days. The activity of GSH reduced in gills and liver in all treatments after all periods due to strong oxidative stress. MDA level increased as a marker of oxidative in gills and liver in all treatments after all periods.