The role of serum lipids [total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG)] in the pathophysiology of mood disorders is not clear. The aim of this study was to determine lipid profiles in patients with affective disorders. The study included medication-free female subjects (41 patients with bipolar disorder, 22 in a manic and 19 in a depressive phase), 34 patients with major depression, and 50 healthy controls. Serum lipid levels were determined using standard laboratory tests. All patients had significantly lower HDL-C values than control subjects. Increased TG levels were found in patients with bipolar disorder compared with healthy subjects. The changes in lipid profiles persisted when data were adjusted for age, smoking and menopausal status. The results revealed no differences in cholesterol and LDL-C levels and body mass index, but significant differences in the ratios of cholesterol/HDL-C and LDL-C/HDL-C (atherogenic index) among groups. Our results suggest that low HDL-C levels and a high atherogenic index might be a hallmark of affective disorders. Since low HDL-C levels could be a risk factor for the development of coronary heart disease, further investigation of lipid metabolism in affective disorders is warranted.