Circadian preferences may affect the severity and symptom structure of depression and could influence specific symptom clusters of depression. This study aims to examine the relationship between chronotypes and symptomatology in patients with major depression. One hundred and one drug-naive outpatients with major depression were evaluated through the use of the Hamilton Rating Scale for Depression (HRSD). The Morningness-Eveningness Questionnaire (MEQ) was used to the define chronotypes and the quality of subjective sleep was measured with Pittsburgh Sleep Quality Index (PSQI). The medical records of patients were evaluated retrospectively to determine the presence of another medical illness. HRSD total score and cognitive and vegetative factor scores were significantly higher in the evening chronotype than in the morning and intermediate chronotypes (p < .001). In the regression analysis, MEQ total score was inversely related to HRSD-vegetative factor score (p < .001). The ratio of comorbid illness was found to be statistically significant among depressed patients with evening chronotype (p = .001). Additionally, binary logistic regression analysis was performed to ascertain the likelihood of participants having comorbid medical illness; only age (p = .010) and MEQ total score (p = .011) were associated with exhibiting comorbid illness. General and psychiatric clinical examinations need to be considered with the understanding of circadian preference.