To estimate the economic burden of tuberculosis treatment in Sistan, the region with the highest number of tuberculosis cases in Iran. All patients with smear-positive pulmonary tuberculosis who had contracted tuberculosis in 2018 and successfully completed their treatment were interviewed. Ninety patients with a mean age of 57 ± 18 years were interviewed. Most of them were women (58%), housewives (57%) and resided in rural areas (84%). The mean cost of treatment for tuberculosis was estimated as 6800 USD per patient. Direct costs were 87% of the total cost. Twenty-two patients lost an average income of 530 USD (8514590 rials) during treatment. The results showed the significant correlation of direct and indirect costs with sex, age, place of residence and education (P < 0.05). It appears essential to improve social protection and implement interventions to promote knowledge in rural areas.