Addiction is one of the world's major health problems with large direct health costs (psychiatric and physical). The present study aimed to investigate the oxidative stress effects of heroin and cannabis addiction and their impact on the immune system. Eighty four subjects (60 addicts and twenty four control subjects); their ages ranged from 18 to 38 years were studied. Each subject was screened for detection of substance of abuse in urine and detection of cytokines; interleukins (IL2 and IL6) and reactive oxygen species (ROS) (reduced glutathione; thiobarbituric acid reactive substances {TBARS} and protein oxidation) in blood after taking informed consent. The results revealed a significant decrease in serum IL-2 and in protein thiols level in males and females heroin and cannabis addicts (p < 0.001). While, there were significant increase in both TBARS and protein oxidation in heroin and cannabis male and female addicts in comparison to the control group. It could be concluded that heroin and cannabis addiction had deleterious effects on the immune system through their effects on oxidative stress and release of ROS. Keywords: Addiction, oxidative stress; interleukins, lipid peroxidation, protein oxidation, ROS.