Background: Tuberculosis (TB), is one of the major common air born infectious bacterial diseases which remains a major worldwide health problem with global mortality. Objective: To evaluate the efficiency of serum samples compared to sputum for the early diagnosis of TB, and to evaluate the levels of superoxide dismutase (SOD), catalase (CAT), total antioxidant status (TAS) and tumor necrosis factor- (TNF-) in patients with pulmonary tuberculosis (PTB). Methods: One hundred patients with clinically suspected PTB and 25 healthy individuals were enrolled in the study. According to the bacteriological results, 78 patients were diagnosed as having PTB infection. These cases were categorized into 69 culture positive cases [sputum and serum PCR positive patients (n=42), sputum PCR positive and serum PCR negative patients (n=16) and sputum and serum PCR negative patients (n=11)] and 9 culture negative and sputum PCR positive cases with radiological lung abnormalities suggestive for PTB. For these 78 cases, erythrocyte SOD, CAT, serum TAS and TNF- were determined. Twenty two patients were culture negative and negative for both sputum and serum PCR. They had no PTB and were not involved in biochemical studies. Results: In all 78 PTB patients, erythrocyte SOD, CAT and serum TAS levels were statistically lower than controls (p<0.05), while TNF- was highly significantly increased (p=0.001). There was a significant direct linear correlation between SOD and CAT and TAS (p<0.0001, r= 0.78; p<0.0001, r= 0.88; p<0.0001, r=0.80 respectively) and a significant reverse linear correlation between TNF- and SOD, CAT and TAS level (p<0.0001, r=-0.55; p<0.0001, r=-0.51; p<0.0001, r=-0.65 respectively). Conclusion: Although the sputum culture is still the gold standard for the diagnosis of patients with PTB, sputum PCR is an efficient method that could be used as an alternative to the culture for the rapid identification of PTB cases. The lower levels of SOD, CAT and TAS may be improved by the antioxidant therapy which may help in better prognosis. Anti TNF-α therapy may help in decreasing the elevated level of TNF-α shown in all PTB patients.