Depression is the third leading cause of morbidity and mortality worldwide and expected to be the first one by 2030. Its relation to micronutrients is addressed sufficiently in adults. However, the studies in adolescence are scarce. The aim of the work: assessing serum levels of vitamin B12, folate, homocysteine, and vitamin D levels in adolescents with depressive disorder. Methodology: One hundred adolescents [12-18 years] with diagnosis of anxiety or depression were included in the study. Another 100 age and sex matched healthy children were included for comparison. Data were collected through detailed interviews for the adolescent and his/her family. The data collecting methods included the Children’s Depression Inventory [CDI], and State-Trait Anxiety Inventory 1 and 2 [STAI-1 and STAI-2 anxiety scales] applied. Serum levels of vitamin B12, vitamin D, folate and homocysteine were measured. Results: The patient group had significantly lower vitamin B12, folate and vitamin D levels when compared to healthy adolescents. Otherwise, homocysteine levels were significantly higher among patients than healthy adolescent groups. The CDI, STAI- I and II were inversely correlated with folate, vitamin B12 and vitamin D. but correlated positively with homocysteine was propitiate. Multiple linear regression analysis revealed that, folate, vitamin D, vitamin B12 and homocysteine remain significantly associated with disease severity [CDI]. However, only vitamin B12 was significantly associated with STAI-I and II. Others not significantly associated. Conclusion: Vitamin B12, folate and vitamin-D deficiency with hyperhomocysteinemia were correlated with the development and severity of anxiety or depression. Vitamin B12 was the powerful contributing substance even after controlling for others.