Glycosylation, the addition of a carbohydrate moiety to a protein during biosynthesis, is a common post-translational modification involved in several disease states. Specific protein-glycan structures have been reported to be useful as biomarkers for cancer and some neuropsychiatric disorders; however, the relationship between glycosylation of plasma proteins and major depressive disorder (MDD) has not been studied. This study aimed to determine whether the plasma protein-glycan structure would differ in MDD from typical values, using both a stress-based mouse model and samples from patients with MDD. The glycan structure profile of plasma proteins might represent candidate biomarkers for MDD.