Little attention has been given to the role of antibodies against Mycobacterium tuberculosis (Mtb) infection. We have compared the levels of IgA and IgG against ESAT-6/CFP-10 and Rv2031c antigens in sera of culture-confirmed pulmonary tuberculosis (PTB) patients, healthy Mtb infected and non-infected individuals in endemic TB settings. Venous blood samples were collected from 166 study participants, sera were separated and assayed by an enzyme-linked immunosorbent assay (ELISA). QuantiFERON-TB Gold In-Tube (QFTGIT) assay was used for the screening of latent TB infection. The mean optical density (OD) values of IgA against ESAT-6/CFP-10 and Rv2031 were significantly higher in sera of patients with culture confirmed PTB compared to healthy Mtb-infected and non-infected individuals (p<0.001). The mean optical density (OD) values of IgG against ESAT-6/CFP-10 and Rv2031 were also significantly higher in sera of patients with culture confirmed PTB compared to healthy Mtb-infected and non-infected individuals (p<0.05). The mean OD values of IgA against both antigens were also higher in sera of healthy Mtb-infected cases compared to non-infected individuals. There were positive correlations (p<0.05) between the level of IFN-γ induced in QFTGIT assay and the OD values of serum IgA against both antigens in healthy Mtb-infected subjects. The current study shows the potential of IgA response against ESAT-6/CFP-10 and Rv2031 antigens in discriminating clinical TB from healthy Mtb-infected and non-infected cases. Nevertheless, further well designed cohort study is needed to fully realize the full potential of this diagnostic marker. This article is protected by copyright. All rights reserved.