Abstract: Mazandaran province, in the North of Iran, has a high prevalence of thalassemia and depression is a known complication in thalassemic patients like in many other patients with chronic diseases. Much of evidence associating thalassemia and depression has come from descriptive studies and is often inconsistent in its conclusion. This study reports the findings of an Iranian study concerning the relationship between thalassemia and depression. The population of the study was a cohort of 165 thalassemic patients (86 girls and 79 boys), who came to Booali Sina Hospital in Sari, all aging 9-16 years and 201 matched controls. Children Depression Scale was used to investigate depression among them. Rate of depression in thalassemic patients was significantly higher than the control group (14 vs. 5.5%), although the mean depression score was higher in girls of control group than in girls who suffered from thalassemia. Presented data suggest that all patients with thalassemia major and intermedia should undergo depression assessment so that suitable interventions can be implemented.