Although multidrug therapy (MDT) has been widely used for the treatment of leprosy for nearly 40 y, the disease remains a public health concern in some areas. The early detection of leprosy cases is vital to interrupt Mycobacterium leprae transmission, but currently diagnosis is typically achieved during the recognition of clinical symptoms by professional staff performing physical examinations in conjunction with microbiological assessment of slit skin smears (SSSs) and histopathology. In the last 10 y, serum antibody detection tests have emerged to aid leprosy diagnosis. Here we evaluated the ability of antigens NDO-BSA and LID-1 (ML0405 and ML2331) and the conjugate of these, NDO-LID, to detect antibodies in the sera of 113 leprosy patients and 166 control individuals in Yunnan province in southwest China. We found that each antigen was readily detected by sera from multibacillary (MB) patients, with sensitivities of 97.3%, 97.3% and 98.6% for NDO-BSA, LID-1 and NDO-LID, respectively. Even among paucibacillary (PB) patients the antigens detected antibodies in 74.4%, 56.4% and 69.2% of serum samples, respectively. Receiver operating characteristics (ROC) curve analysis indicated that, irrespective of the leprosy case classification as MB or PB, the detection efficiency obtained with NDO-LID was better than that obtained with the other two antigens (with LID-1 being a slightly better than NDO-BSA). Our results indicate the utility of NDO-LID in assisting in the diagnosis of PB and MB leprosy patients and that these antibody detection assays represent powerful diagnostic tools. We suggest that could be implemented into the procedures of local health centres in leprosy-endemic regions to assist in earlier diagnosis.