Objective: Sleep, physical activity, and social domains of biological rhythm disruptions may have specific effects on the symptom cluster and severity of depression. However, there is a lack of structured clinical evaluation to specify the domains of biological rhythms in patients with depression. Methods: Ninety drug-naïve subjects with depression and 91 matched healthy controls were recruited for the study. The severity of depression was examined with the Hamilton Rating Scale for Depression (HRSD), while biological rhythm was evaluated using the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN). Results: Patients with depression showed significantly greater biological rhythm disturbances than healthy controls in all domains of BRIAN (sleep, activity, social, and eating). BRIAN-Total correlated positively with HRSD-Total and HRSD-Total without sleep cluster. The sleep and activity domains correlated significantly with HRSD-Total score. Additionally, the sleep, activity, and social domains correlated significantly with HRSD-Total without the sleep cluster score. Regression analysis revealed the activity (β = 0.476, t = 5.07, p<0.001) and sleep (β = 0.209, t = 2.056, p = 0.043) domains may predict HRSD-Total score. Conclusion: Consideration of biological rhythm domains in clinical examination and focusing on the sleep and activity domains may hold promise for the management of depression.