Chronic psychosocial stress is a significant risk factor for the development of stress-associated psychiatric disorders, including major depressive disorder, which causes profound debilitation and has increasing worldwide prevalence. Pre-clinical and clinical studies have linked peripheral immune system alterations to stress-related disorders, such as elevated levels of proinflammatory immune cells and cytokines in circulation. Endothelial cells are critical components of the blood-brain barrier (BBB), as they interface directly with immune cells and their released factors, which can enter the brain parenchyma to regulate local neural activity. Research suggests region-specific differences in brain endothelial permeability, which may be related to differences in the local production of chemoattractants and adhesion molecules for immune cells after chronic psychosocial stress. However, a causal mechanistic understanding of how these changes occur in stress-responsive brain regions, including the nucleus accumbens (NAc), is not fully demonstrated. To address this gap, endothelial cell mRNA was collected from the NAc of male mice following chronic social defeat stress (CSDS) using translating ribosome affinity purification. Following RNA sequencing and analysis, we observe that CSDS strongly affects NAc endothelial cells, such that stress-susceptible male mice display increased expression of genes associated with endothelial cell junction organization and adhesion. Current work aims to validate the upregulation of these genes and virally manipulate their expression to determine their involvement in immune cell recruitment to the endothelium and BBB permeability. This work will uncover unique mechanisms through which endothelial cells respond to chronic stress and provide insight for developing novel therapeutics for stress-associated psychiatric disorders.