Objective: To evaluate the health-related quality of life (HRQOL) of patients with chronic depression. Methods: The study involved patients with chronic depression being followed-up at an outpatient clinic at a local hospital in Malaysia. HRQOL was assessed using the Sheehan Disability Scale (SDS); while symptom severity was assessed using the Montgomery-Asberg Depression Rating Scale (MADRS). Results: 104 patients of Malay, Chinese and Indian ethnic groups met the selection criteria. Mean total SDS and MADRS scores was 9.36 ± 7.92 and 13.99 ± 11.58 respectively. There were no significant differences of HRQOL scores between the different ethnicities and between males and females. Symptom severity significantly influenced total and component HRQOL scores. Conclusions: The HRQOL of patients with chronic depression was found to be significantly influenced by symptom severity. Data obtained in this study can be used in the design and implementation of therapeutic and preventive interventions.