Major depressive disorder (MDD) is a highly prevalent psychiatric disorder that is associated with physical impairment, medical comorbidity, and mortality worldwide. Although the etiology underlying MDD remains unclear, stressful life events may cause depressive symptoms and the incidence of MDD. Neurotransmitters and their metabolites in the brain play crucial roles in the regulation of mood and emotion. In addition, exposure to stress alters the extracellular levels of these metabolites in the brain. Recently, metabolite levels in the blood have received attention as a possible marker of depression. Therefore, metabolomic alterations in the brain and the blood, especially under the stressful condition, and their relationship is important to resolve the etiology of depression. In this talk, I introduce the recent studies conducting the comprehensive analysis of extracellular metabolites in the brain and blood in mice.