Abstract The authors’ preliminary study selected 22 items for Depression and Somatic Symptoms Scale (DSSS), including depression subscale (DS) and somatic subscale (SS). The aim of the study was to test reliability and validity of the DSSS. The study enrolled 135 consecutive outpatients (34 male and 101 female) experiencing a major depressive episode (the MDE group), 95 of whom (25 male and 70 female) accepted 1 month of treatment (the treatment group). Diagnosis was confirmed by using the Structured Clinical Interview for 4th edition with text revision Diagnostic and Statistical Manual Axis I Disorders. The DSSS and Hamilton Depression Rating Scale (HAMD) were given and evaluated. Cronbach’s alpha was used to assess internal consistency. The correlation between the improvement percentage (IP) for the HAMD and the IP for the DSSS was calculated for the treatment group. Factor analysis was performed by using the principal-axis factoring method with promax rotation. Cronbach’s alpha values of the DSSS and its subscales ranged from 0.73 to 0.94. Pearson correlation coefficients for the relationship between the DSSS and HAMD ranged from 0.63 to 0.86. In the treatment group, DSSS and HAMD scores were significantly decreased after treatment and the IP for the HAMD and the DSSS were similar and correlated (correlation coefficient = 0.78). The results of the factor analysis demonstrated that most of the items in DS and SS appropriately loaded in Depression and Somatic factors, respectively. The discriminative ability of the DSSS for anxiety comorbidities was not inferior to that of the HAMD. Therefore, the DSSS is reliable and sensitive to the treatment and has acceptable convergent, factorial, and distinct-groups validities. Because it assesses both depression and somatic symptoms, DSSS may overcome the deficiency of other depression scales with few somatic items.