To explore the pathophysiology of food intake and weight change in depression, we decided to measure serum ghrelin and leptin levels, lipid profile and body mass index (BMI). Twenty-eight outpatients with Major Depressive Disorder (MDD) and 20 healthy controls enrolled in this study. The patients were asessed by structured clinical interview for DSM-IV and Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) were also administered to all patients. BMI was calculated for all subjects. After the patients and controls fasted overnight, venous blood samples were drawn from antecubital vein in the morning at a single time point. We found higher serum ghrelin levels in patients with MDD than those in controls, but leptin did not show any significant difference as well as body mass index, age, and gender. There was a negative correlation between the ghrelin and HDL-cholesterol levels in patients with MDD. However, serum ghrelin levels did not show any correlation with leptin, BMI, duration of illness, gender, age, and lipid profile. In conclusion, although the groups have been matched for gender, age and BMI, increased ghrelin but not leptin levels seem to be associated with the patients with MDD.