© 2020 The Nordic Psychiatric Association.Background: Major depressive disorder (MDD) is a mental health and emotional disorder that affects children and adolescents worldwide. This study aimed to evaluate serum nesfatin-1, ghrelin, and lipid levels as biological markers of adolescent MDD and their relationship with the severity of depression-anxiety and suicide risk in MDD. Methods:This study included 37 drug naïve adolescents between the ages of 12 and 18 who were diagnosed with a first episode MDD according to the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL) and DSM-V diagnostic criteria. Thirty-three healthy adolescents between the ages of 12 and 18 were included as the control group. The Children’s Depression Inventory (CDI), Screen for Child Anxiety Related Disorders (SCARED), and Suicide Probability Scale (SPS) were used to evaluate the subjects in the MDD and control groups. In the first stage, serum nesfatin-1, ghrelin, and lipid levels were compared between the adolescents diagnosed with MDD and the control group. Next, the correlations between these levels and the CDI, SCARED, and SPS scores were evaluated. Results: Nesfatin-1 levels were significantly lower in the MDD group than the control group (p < 0.001) A positive correlation was found between the nesfatin-1 levels and the SPS scores. Conclusions: This is the first study to evaluate nesfatin-1 levels in adolescent depression, suggesting that nesfatin-1, ghrelin, total cholesterol, and low-density lipoprotein cholesterol (LDL) levels can be used as biomarkers in child-adolescent MDD. However, it is evident that further studies with larger samples and post-treatment measurements are needed.