Waterpipe (narghile) smoking with moassal type of tobacco is common in the Lebanese population and may result in health problems. This study investigated the effects of water pipe (narghile) smoking on oxidative stress in lungs and liver of mice and the potential protective effect of selenium administration. A number of 24 mice were divided equally into four groups (i) The control group received no exposure or treatment; (ii) mice exposed to waterpipe smoke for 15 minutes/day every other day for 4 times within 8 days; (iii) mice exposed to smoke and receiving intraperitoneal injection of 1.3 μg sodium selenite/kg body weight 15 minutes before exposure to smoke and (iv) mice exposed to smoke and receiving intraperitoneal injection of 3.9 μg sodium selenite/kg body weight minutes before exposure to smoke. The mice were sacrificed after 8 days of exposure and liver and lungs were harvested. MDA and NO levels were significantly higher in the liver and lungs, while the activities of SOD and GPx-1 decreased significantly in mice exposed to waterpipe smoke as compared to control group. The activity of CAT in lungs decreased significantly in the smoke exposed group at P < 0.05. Treating mice with 3.9 μg sodium selenite/kg body weight decreased MDA in lungs and liver and NO in lungs while increased significantly the activities of SOD, GPx-1 in both lungs and liver and the activity of CAT in lungs of mice at P <0.05. Histological examinations confirmed these biochemical effects in smoke exposed mice and smoke exposed mice treated with selenium. In conclusion, waterpipe smoke resulted in increased lipid peroxides and decreased activities of antioxidant enzymes SOD, GPx-1 and catalase in the lungs and liver of mice. Treatment of mice with 3.9 μg sodium selenite/kg body weight 15 minutes before exposure to smoke restored the levels of these parameters.