Abstract Body: Introduction: Soldiers experience a unique stress environment that compounds particulate matter (PM) and psychosocial exposures. Previous literature often assesses these factors independently, failing to recapitulate the complete landscape of war. We hypothesized mice exposed to simulated combat for 10 days prior to- or with PM exposure may enhance cardiovascular stress. Methods: Male C57/BL6 mice were exposed to either filtered air (FA) or fine particulate matter (PM_2.5; 15.7 μm×m^-3) for 3 weeks. A subset also experienced social defeat stress (Stress-only; 10-min of fighting for 10 d) or social defeat either prior to PM_2.5 exposure (Pre-stress avg: 13.9 μm×m^-3) or concurrently during the final 10 days of PM_2.5 exposure (co-exposure; avg: 26.7 μm×m^-3). Blood pressures were assessed before and immediately after exposures via tail-cuff plethysmography. Echocardiography was performed 24 h after exposure and followed by blood collection for corticosterone via ELISA. Cardiac pressure-volume (P-V) loops were performed 72 h later and tissues stored for later analysis via qPCR. Where appropriate, data were analyzed via one-way ANOVA across exposure level and compared against FA controls via Sidak’s test. Results: Pre-stress induced a thinning of left ventricular walls (LVAW;s, LVAW;d, LVPW;s and LVPW;d, all p<0.05) and increased chamber diameters (LVID;s p=0.01; LVID;d p=0.05). Following PM alone and Co-exposure, mean arterial pressures were decreased (both p<0.01). Cardiac P-V loops indicated Pre-stress had reduced ejection fraction (%; p=0.01) despite elevated stroke volumes (p=0.05). In the lungs, the Pre-stress group showed reduced inflammatory and fibrotic gene expression (Il1b and Tgf1b, both p<0.05); however, pro- and anti-apoptotic genes were reduced (BAX and BCL-2, both p<0.05). In contrast, the Stress-only group had increased left ventricle BAX, and BAX/BCL-2 (both p<0.01) gene expression ratios and Tgf1b (p<0.01). The Stress-only and Co-exposure groups both showed reduced corticosterone levels (both p<0.05) that were unaltered in the Pre-stress group. Conclusion: Collectively, these data suggest that combined exposure to psychosocial stress and PM is recapitulate a pre-clinical model of warfighter-related disease.