Background: Tuberculosis (TB) still remains a major cause of morbidity and mortality worldwide. In Nigeria, there is little information on antioxidant status of TB patients. In this study, effects of oxidative stress markers and vitamins C and E were investigated in pulmonary TB patients attending a health care facility in Nigeria. Methods: Sputum specimens were processed for acid-fast bacilli (AFB) while rifampicin resistance was determined by GeneXpert/Rif assay. Patients were screened for HIV after adequate counselling. Assays for hydrogen peroxide (H 2 O 2), malondialdehyde (MDA), protein carbonyl (PC), myeloperoxidase (MPx), xanthine oxidase (XO), catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), glutathione S-transferase (GST), glutathione peroxidase (GPx), α-tocopherol and ascorbic acid were estimated using standard methods. Results: Of the 83 recruited subjects, 29 (34.9%) were AFB negative, 30 (36.1%) were AFB positive while 24 (29.0%) were positive for rifampicin resistance. Overall, HIV prevalence was 6.0% while higher rate of 16.7% was found among the rifampicin resistant subjects. Plasma concentrations of H2O2, MDA and PC and also MPx and XO activities were significantly higher among rifampicin resistant subjects compared with AFB positive and AFB negative groups (P < 0.05). Plasma concentration of GSH and the activities of SOD, GST and GPX were significantly reduced in rifampicin resistant subjects compared with the 2 other groups (P < 0.05). The plasma activity of CAT was similar between rifampicin resistant and AFB positive subjects but significantly lower when compared with AFB negative group. Rifampicin resistant subjects had significantly lower concentrations of α-tocopherol and ascorbic acid compared with 2 other groups (P < 0.05). Conclusion: This study revealed that resistance of TB patients to rifampicin may be due to induction of oxidative stress. Administration of vitamins C and E may be beneficial by reducing the severity of the disease.