Exosomes are small (30-100 nm) vesicles of the endocytic membrane that may be found in the endosome system of multivesicular organs and are released after fusion of multivesicular bodies with the plasma membrane. Exosomes function as carriers for specific loads and are stable in biological fluids; hence, exosomes are considered as potential biomarkers of different diseases. The degree of involvement and functional significance of exosomes in pathogenesis of depression have been poorly studied. The development of diagnostic methods for depressive disorders based on the analysis of circulating exosomes is very promising, despite the methodological complications related to their isolation and identification. The purpose of this study was to isolate exosomes from the blood serum of patients with major depressive disorder (MDD) and compare them with healthy volunteers using different methods of evaluation. The concentration of serum exosomes assessed using the methods of dynamic light scattering, nanoparticle tracking analysis, and the enzyme-linked immunoassay was statistically elevated in patients with MDD compared to healthy volunteers. The possible connection between the increased level of serum exosomes with the cell-mediated immune activation that is seen in depression is discussed.