Water pollution has been a major concern for agrarian societies like Pakistan. Pharmaceutical industries are amongst the foremost contributor to industrial waste. Present study addresses the generation of oxidative stress caused by 2 months exposure to pharmaceutical wastewater in rats and their response to oral treatment with vitamin E, a potent antioxidant. The rats were randomized into five groups (n = 5) named as negative control, pharmaceutical wastewater (PEW) 100 %, PEW 10 %, PEW 1 %, and PEW 100 % + vitamin E. Oxidative damage in rats was evaluated by estimation of the activities of total superoxide dismutase (T-SOD), catalase (CAT), and the concentration of hydrogen peroxide (H2O2) in the liver, kidney, and blood/plasma. Exposure to pharmaceutical wastewater significantly decreased the activities of T-SOD and CAT and concentration of H2O2 in the liver and kidney and blood/plasma. Exposure to 100 % pharmaceutical wastewater exhibited a maximum decline in T-SOD activity, and activity was reduced to only 63.57 U/mL, 32.65, and 43.57 U/mg of protein in the plasma, kidney, and liver, respectively. Exposure to wastewater minimized activity CAT to 89.25 U/g of hemoglobin, 54.36, and 62.95 U/mg of protein in the blood, kidney, and liver, respectively. Treatment with vitamin E significantly increased the activity of T-SOD and CAT. However, increase in concentration of H2O2 was also observed in vitamin E exposed rats. Histopathology of the kidney revealed coagulative necrosis of renal epithelial cells and peritubular congestion. Endocardium showed infiltration of inflammatory cells and cellular breakdown in some areas. Lung sections exhibited atelectasis and emphysema of alveoli suggesting decline in lung function. The anatomy of the liver was also compromised due to severe degeneration and cellular swelling. The present study concluded that pharmaceutical wastewater induced severe oxidative stress in Wistar rats and ensued in histopathological lesions in several vital organs suggesting its high toxicity. Non-enzymatic antioxidant vitamin E may ameliorate oxidative stress induced by pharmaceutical wastewater.