Appetite, food intake and weight are frequently altered in psychiatric disorders such as major depression and schizophrenia. The few studies investigating weight and the body mass index (BMI) have yielded variable results. Leptin, a fat cell-derived hormone signalling to the brain the size of the adipose tissue, plays a pivotal role in the regulation of weight and food intake. Moreover, leptin is involved in the control of other behaviors and in brain development. There is almost no information about the amounts of circulating leptin in major depression or schizophrenia. We investigated the BMI and plasma leptin levels in patients with major depression (n = 62), schizophrenia (n = 42), and in healthy controls (n = 64). Mean BMIs did not differ between groups. However, leptin levels were significantly lower in both patient groups compared to healthy controls. Moreover, patients suffering from schizophrenia showed significantly lower leptin levels than depressed patients. Decreased leptin levels were independent of psychotropic medication. We conclude that depression and schizophrenia go along with decreased systemic leptin concentrations that cannot be explained by medication or an altered BMI. Hence, leptin might play an important pathophysiological role in these psychiatric disorders that deserves further scientific attention.