Abstract Recent studies suggest that the dysfunction of neural plasticity is associated with mood disorders. Hypoxia-inducible factor-1 (HIF-1), which is a transcriptional activator of vascular endothelial growth factor (VEGF), activates the cellular response to hypoxia. HIF-1 is ubiquitously expressed in all cells, including peripheral leukocytes. However, little is known about the role of HIF-1 in mood disorder. In the present study, we investigated the mRNA expression levels of HIF-1 (α and β) and its target genes (VEGF, GLUT1, PGK1, PFKFB3, and LDHA) in the peripheral white blood cells of patients with major depressive disorder (MDD) and bipolar disorder (BPD). We found increased expression of HIF- 1α and HIF-1β mRNA, as well as the target genes, VEGF, and PFKFB3 in both MDD and BPD patients in a depressive state compared to healthy control subjects. Furthermore, the mRNA expression levels of GLUT1, PGK1, and LDHA were increased in MDD patients in a depressive state compared to healthy control subjects. We also found increased expression of HIF-1α and LDHA mRNA in MDD patients in a remissive state, whereas the mRNA expression levels of other genes in a remissive state were comparable to those in healthy control subjects. There was no significant difference in mRNA expression levels of the genes examined among patients receiving any type of antidepressant or mood stabilizer. Our data suggest that altered expression of HIF-1 and its target genes mRNA in peripheral blood cells are associated—mainly in a state-dependent manner—with mood disorders (especially with MDD). In addition, altered expression of HIF-1 and its target genes may be associated with the pathophysiology of depression.