Long-term depression may increase the risk for adverse coronary events. Low levels of high-density lipoprotein cholesterol (HDL-C) have in particular been suggested to underlie this connection. A total of 124 participants with a recorded seven-year history of depressive symptoms (depressed, n=63) or euthymic state (controls, n=61) underwent a Structured Clinical Interview for DSM-IV to confirm their psychiatric diagnosis. Total cholesterol (TC), HDL-C and low-density lipoprotein cholesterol (LDL-C) levels, triglycerides, non-HDL-C and atherogenic indices (LDL-C/HDL-C and TC/HDL-C) were assessed. The HDL-C levels were lower and atherogenic indices higher in the depressed group compared with the controls. Furthermore, those with HDL-C level below the gender-adjusted median (<1.54 mmol/l in women, <1.16 mmol/l in men) were 2.4-fold more likely to be depressed in a model adjusting for age and non-HDL-C (p=0.019). After further adjustment for educational level, marital status, alcohol use, daily smoking and overweight this association remained significant (p=0.049). These findings suggest that compared with the healthy controls, those with long-term depression may have lower HDL-C values and higher atherogenic indices.