Background The voice carries various information produced by vibrations of the vocal cords and the vocal tract. Though many studies have reported a relationship between vocal acoustic features and depression, including mel-frequency cepstrum coefficients (MFCCs) which applied to speech recognition, there have been few studies in which acoustic features allowed discrimination of patients with depressive disorder. Vocal acoustic features as biomarker of depression could make differential diagnosis of patients with depressive state. In order to achieve differential diagnosis of depression, in this preliminary study, we examined whether vocal acoustic features could allow discrimination between depressive patients and healthy controls. Methods Subjects were 36 patients who met the criteria for major depressive disorder and 36 healthy controls with no current or past psychiatric disorders. Voices of reading out digits before and after verbal fluency task were recorded. Voices were analyzed using OpenSMILE. The extracted acoustic features, including MFCCs, were used for group comparison and discriminant analysis between patients and controls. Results The second dimension of MFCC (MFCC 2) was significantly different between groups and allowed the discrimination between patients and controls with a sensitivity of 77.8% and a specificity of 86.1%. The difference in MFCC 2 between the two groups reflected an energy difference of frequency around 2000–3000 Hz. Conclusions The MFCC 2 was significantly different between depressive patients and controls. This feature could be a useful biomarker to detect major depressive disorder. Limitations Sample size was relatively small. Psychotropics could have a confounding effect on voice.