Background: Wasting is a prominent feature of tuberculosis and may be more severe among individuals with HIV coinfection. It is likely that several biological mechanisms, including the anorexia of infection, are contributing to wasting. Objective: The purpose of this study was to determine whether leptin concentrations, in relation to the inflammatory cytokine response and level of HIV infection, are contributing to loss of appetite and wasting in adults with pulmonary tuberculosis and HIV infection. Design: We characterized plasma leptin concentrations in relationship with self-reported loss of appetite, body mass index, fat mass (FM), IL-6, and HIV load in a cross-sectional study of 500 adults who presented with pulmonary tuberculosis in Zomba, Malawi. Results: Plasma leptin concentrations, associated with FM, significantly decreased by increasing tertile of plasma HIV load (P = 0.0001). Leptin concentrations were inversely associated with plasma IL-6 concentrations after adjusting for sex, age, FM, and HIV load. Plasma leptin concentrations were associated with neither loss of appetite nor wasting. Inflammation, reflected by increased IL-6 concentrations, was associated with loss of appetite (odds ratio, 3.41; 95% confidence interval, 1.91-6.09), when adjusted for sex, age, FM, leptin concentrations, and HIV load. A high plasma HIV load was associated with severe wasting, defined as body mass index less than 16.0 kg/m(2) ( odds ratio, 2.14; 95% confidence interval, 1.09-4.19) when adjusted for sex, age, IL-6, FM, and leptin concentrations. Conclusion: This study suggests that the anorexia and wasting seem primarily determined by the level of inflammation and the level of HIV infection in patients with tuberculosis and HIV coinfection.