Melioidosis, caused by Burkholderia pseudomallei, has variable manifestations. The disease can present as an acute or a chronic form or localized or disseminated or can remain latent for many years. Acute septicaemic melioidosis has a high fatality rate when untreated and therefore, an early diagnosis is critical. Lack of testing facilities and of an awareness of the manifestations of the disease makes it likely that it is underreported in India. A sonicate and a lipopolysaccharide (LPS) antigen were evaluated by an IgM enzyme immunoassay in patients with culture-confirmed melioidosis (n = 29), fever of unknown origin (n = 214) and healthy controls (n = 109). Patients with melioidosis had significantly higher optical density values than both control categories, but the sensitivity of both tests was low (25% for sonicate, 62% for LPS). These data highlight the problems with serodiagnosis in endemic settings, where high cut-off values are required for specificity, and result in low sensitivity.