BACKGROUND: Nesfatin-1 (NF-1) is a parameter that has been shown to have an important potential in the modulation of the emotional state such as depression. The study focused to investigate the relationship between the plasma NF-1 level and depression. SUBJECTS AND METHODS: Seventy-three patients who have a major depressive disorder (MDD) and 71 healthy individuals participated in the study. Plasma NF-1 was analyzed by Enzyme Linked Immunosorbent Assay (ELISA) and compared according to the groups. RESULTS: The mean NF-1 was lower in the patients with MDD than being in the healthy (p:0.019). Plasma NF-1 level was statistically significantly lower in the overweight MDD than in the non-overweight MDD (p:0.024). We observed a negative correlation between plasma NF-1 level and age (r:-0.178, p:0.033), BMI (r:-0.212, p:0.011), HAM-D scores (r:-0.185, p:0.026). However, there was no correlation for smoking status in both groups (r:0.095, p:0.259). CONCLUSION: This study demonstrated the relationship between plasma NF-1 level and MDD as well as overweight. Therefore, NF-1 might be related to certain nervous system pathologies as well as adipose tissue in the body.