Objective: The primary aim of our study was to determine the prevalence of psychiatric morbidity in a cohort of consecutive chronic hepatitis patients not receiving antiviral therapy. The secondary aim of our study was to determine if psychiatric morbidity, type of hepatitis, and the level of depression correlated with health-related quality of life (HRQL). Methods: The study was conducted in collaboration with Hepatology and Infectious Disease Clinics at three-major university hospitals. One hundred seven patients who met the criteria for being diagnosed with either chronic hepatitis B or C, had non-cirrhotic compensated liver disease, had not received antiviral treatment in the preceding 6 months, and had no accompanying physical illness were included in the study. The Structured Clinical Interview for DSM-IV Axis I Disorders, the Short Form - 36 for measuring HRQL, and semi-structured interviews for assessing psychosocial variables were used. Sixty-seven healthy adults formed the control group. Results: 43.9% of the patients had hepatitis B, 56.1% hepatitis C. A psychiatric diagnosis was made in 48.6%, of which 15% was depression. No significant difference was found in the rate of psychiatric diagnosis between hepatitis B and hepatitis C patients. Hepatitis B and C patients were found to vary significantly (p < 0.001) from the control group on all subcategories of quality of life criteria. Psychiatric morbidity (mainly depression) was the major variable on lowering HRQL (p = 0.000). Conclusions: Chronic hepatitis B and C patients presented a high rate of psychiatric disorder. HRQL was significantly decreased in patients with psychiatric morbidity.