This study was performed to evaluate the detrimental effects of some synthetic colorants widely used in manufacturing of soft drinks such as caramel IV, sunset yellow and (tartrazine + brilliant blue) at low dose equal to acceptable daily intake (ADI) and high dose equal to 5 times ADI on oxidative stress markers, biochemical parameters, and histopathological alterations of male rats. Results indicated that treated rats with caramel at low and high doses and sunset yellow at low dose did not cause any toxic effects on tested rats. While, treated animals with high dose of sunset yellow and both low and high doses of (tartrazine + brilliant blue) showed significant decrease in body weights and a significant increase in the relative liver and kidneys weights as compared to control. Results also revealed that a significant decreasein some biomarkers; superoxide dismutase (SOD), glutathione peroxidase (GPX), reduced glutathione (GSH) and catalase (CAT) activities and significant increasein malondialdehyde (MDA), aminotransferases enzymes (AST and ALT), alkaline phosphatase (ALP), urea, and creatinine levels in treated rats with high dose of sunset yellow and both low and high doses of (tartrazine + brilliant blue) compared to control. Some histopathological alterations were observed in liver tissues including congested blood vessels, thickened wall bile duct, pyknosis and cellular infiltration. Also, kidney tissues showed blood congestion, hypercellularity of the glomeruli and narrowing of the urinary space. These alterations were found only at a high dose of sunset yellow and both low and high doses of (tartrazine + brilliant blue) compared to control rats.