This study was designed to investigate the molecules apelin and nesfatin-1, their relationship with depression before and after treatment, and whether they can be used as biomarkers. Forty-seven depression patients referred to psychiatric outpatient clinic who were not on treatment and 47 normal healthy volunteers were enrolled in the study. The Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), the Hamilton Depression Rating Scale (HAM-D), and the Clinical Global Impression (CGI) Scale were administered to all participants. Peripheral blood samples were collected following a 12-hour fasting at the beginning and three months after the start of treatment. Serum apelin and nesfatin-1 levels were measured. Of the 47 depression patients, 35 (74.5%) were females and 12 (25.5%) were males. Thirty-one (66%) of the 47 volunteers were females and 16 (34%) of them were males. Age, marital status, occupation and Body Mass Index (BMI) did not differ between the groups. Serum apelin level was significantly higher in the patient group than in the control group. There was no significant difference between the patient group and the control group in terms of serum nesfatin-1 levels. There was no significant difference in serum apelin and serum nesfatin-1 levels after 3 months of treatment. Serum apelin levels were significantly higher than healthy controls at the time of admission and there was no change in apelin levels after 3-months of treatment (antidepressant, antidepressant + electroconvulsive therapy, antidepressant + therapy) despite clinical recovery. Serum nesfatin-1 levels in the patient group were not different from the control group at the time of referral and at the end of 3 months treatment. There was no relationship between serum apelin level and BMI in our study. Serum nesfatin-1 level and BMI were correlated at the time of admission.