Objective The aim was to assess the level of tumor necrosis factor-α (TNF-α) in patients with active pulmonary tuberculosis (TB) and its relation to BMI; different radiological features whether the lesion is minimally, moderately advanced, and far advanced; and to follow-up the level of TNF-α. Background One of the most important and common complaints of patients with TB, which also affects the immune status, is weight loss. When tuberculous infection occurs, a variety of chemokines and cytokines are secreted from infected cells and tissue macrophages. TNF-α increases early in the disease and takes part in the pathogenesis and prevention of mycobacterial infection. Participants and methods Serum TNF-α was measured in 40 newly diagnosed patients as having active pulmonary TB (group I) and 10 controls (group II). Results Serum TNF-α level was significantly higher in patients with active pulmonary TB than in controls, and there was a highly significant negative correlation between TNF-α level and BMI before and after treatment. Serum TNF-α had insignificant positive correlation with grades of Ziehl–Neelsen stain and chest radiography before and after treatment, and the diagnostic cut-off points of TNF-α was found to be 618.1 pg/ml. Conclusion Serum TNF-α level is higher in patients with TB than in controls. TNF-α plays a role in diminishing appetite, in weight loss, and in increased susceptibility to infection.