BACKGROUND: Depression is a significant psychiatric disorder with particularly high prevalence among adolescents. This mental health condition can have severe consequences, including academic failure, social withdrawal, and suicidal behavior. Given the increasing rate of depression in this age group, understanding the underlying biological mechanisms is essential for early detection and intervention. Recent studies have suggested that immune markers play a role in the pathophysiology of depression, prompting further investigation of their potential association with depressive symptoms in adolescents. AIM: To investigate the relationship between immune markers (monocytes, lymphocytes, and direct bilirubin) and the incidence and severity of depression among adolescents. METHODS: This cross-sectional study recruited 145 adolescent patients with depression [male (M)/female (F) = 38/107] from Jiangbin Hospital in Guangxi, Zhuang and 163 healthy controls (M/F = 77/86) from routine health check-ups. Blood samples were collected after an overnight fast. Depression severity was measured using the Zung Self-Rating Depression Scale. The inclusion criteria were age 12-24 years, diagnosis of depressive disorder (ICD-10), and no recent antidepressant use. The exclusion criteria included psychiatric comorbidities and serious somatic diseases. Key statistical methods included group comparisons and correlation analyses. RESULTS: There was a higher prevalence of females in the depression group ( CONCLUSION: The potential role of elevated levels of immune markers in the early detection of depression in adolescents has been highlighted. Therefore, it is necessary to explore further the relationships between these immune markers and depression.