Background: It has been suggested that some micronutrients have antioxidant and immunomodulating effects on the treatment of mycobacterial disease. In this study, we investigated the effect of vitamin E and selenium supplementation on clinical responses in tuberculosis patients. Materials and Methods: Thirty-five patients with pulmonary tuberculosis diagnosed on the basis of a positive sputum smear for acid fast bacilli or culture for Mycobacterium tuberculosis were selected. Serial sputum examinations were performed before the diagnosis and at the end of every 15 days, during two months of therapy; chest X-ray of all patients were also evaluated. In a setting of double-blind, placebo-controlled trial, the patients were divided into two groups. Group I(n=17) received combination of vitamin E and selenium which composed of 140 mg of α-TE and 200 µg selenium per day, and group II received placebo. All patients in both groups received the same antituberculosis standard therapy. Clinical examination and assessment of micronutrient levels were carried out before and after 2 months of intervention. Results: In group I, elimination of tubercle bacilli from sputum occurred earlier than in group II (6 weeks versus 8 weeks, respectively; p= 0.001). At the end of the 2nd and 6th month of therapy, the median reduction in cavity surface area on chest X-ray in group I was significantly more than group II (2nd month: 1.5(0.0-4.5 versus 9.0(4.0-18.0);p= 0.03, and 6th month: 0.0(0.0-2.3) versus 6.3(1.0-15.8); p <0.05, respectively). Conclusion: Vitamin E plus selenium supplementation may improve the microbiological and radiological outcomes of the treatment in patients with pulmonary tuberculosis. (Tanaffos 2006; 5(2): 49-55)