Abstract Background/Introduction Psoriasis has been associated with vascular and myocardial dysfunction through mechanisms of inflammation and oxidative stress. Purpose We aimed to evaluate sublingual microvascular perfusion and glycocalyx barrier properties in psoriasis patients, as well as their correlation with coronary microcirculatory function and markers of myocardial deformation and atherosclerosis (carotid intima-media thickness, cIMT). Methods We examined 297 patients with psoriasis and 150 controls, adjusted for age, sex, and atherosclerotic risk factors. Perfusion boundary region (PBR), a marker of glycocalyx barrier function, was measured non-invasively in sublingual microvessels with a diameter ranging from 5–25μm using a dedicated camera (Sidestream Dark Field imaging, Microscan, GlycoCheck). Increased PBR indicates reduced glycocalyx thickness. Indexes of microvascular perfusion, including red blood cell (RBC) filling percentage and functional microvascular density, were also calculated. We measured coronary flow reserve (CFR), cIMT and markers of myocardial deformation by speckle tracking imaging utilizing echocardiography [peak twisting, the percentage changes between peak twisting, and untwisting at mitral valve opening (%dpTw-UtwMVO), at peak (%dpTw-UtwPEF), and the end of early LV diastolic filling (%dpTw-UtwEDF)]. Results Psoriasis patients had higher PBR5–25 compared to controls (2.13±0.29 versus 1.78±0.25μm, p<0.05). There was an inverse association of PBR5–25 with perfused microvascular density (r=−0.42, p<0.001) and RBC fraction (r=−0.80, p<0.001). In psoriatic population, PBR5–25 was inversely correlated to CFR (r=−0.30, p=0.045). Increased values of PBR5–9 were associated with reduced untwisting at the end of the mitral inflow E wave (r=−0.24, p=0.006) and reduced %dpTw-UtwMVO (r=−0.35, p<0.001). Furthermore, decreased RBC filling percentage and perfused microvascular density were related to worse LV longitudinal strain and increased cIMT (p<0.05). Finally, a positive correlation between perfused microvascular density and %dpTw-UtwMVO was observed in patients with psoriasis (p<0.05). Conclusion Endothelial glycocalyx thickness is reduced in patients with psoriasis and is associated with impaired coronary and myocardial function, and vascular atherosclerosis. Funding Acknowledgement Type of funding sources: None.