Adiponectin is the most abundant adipose-derived plasma protein. Recently adiponectin levels have been linked to most variables of metabolic syndrome and conventional risk factors for cardiovascular disease. However, its relation with major depression is yet unclear. We evaluated plasma adiponectin levels in 32 first-episode drug-naïve major depression (DSM-IV-TR) patients without conventional risk factors for cardiovascular disease and 32 matched healthy subjects. Major depression patients displayed lower adiponectin plasma levels compared to controls (P<0.01). Adiponectin significantly correlated with depression severity, as assessed by HAM-D (rho=0.83, P<0.001). This study shows decreased plasma adiponectin concentrations in major depression patients and relates adiponectinemia reduction to major depression severity.