Abstract Body (Do not enter title and authors here): Background: Endothelial glycocalyx (eGC) is a layer of glycosaminoglycans adhered to proteoglycans that cover the inner surface of the vessels. The integrity of this structure sustains some vascular properties such as shear stress-induced nitric oxide release and the prevention of platelets and neutrophils adhesion on the vessel surface. eGC shedding could contribute to atherosclerotic plaque vulnerability and acute myocardial infarction (AMI) installation. This research investigated whether acute eGC damage and microvascular dysfunction occurred during AMI. Methods: Sublingual microcirculation was assessed through Capiscope HCVS Handheld Video Capillaroscopy System (KK Technology, Honiton, UK) during the first 72h of hospital admission because of ST-elevation AMI (before) and repeated around six months later (after). All images were automatically analyzed using the GlycoCheck (Alpine, UT, USA), which estimated the perfused vascular density (PVD), the red blood cell (RBC) filling of the vessels, the perfused boundary region (PBR) in µm, an inverse parameter of the eGC thickness; and the microvascular health score (MVHS). This score ranges from 0-10; the lower its numerical value, the greater the microvascular impairment. Results: Twenty patients were included (61±10 years old, 85% males, 55% anterior AMI, 70% hypertension, 25% diabetes, 45% current smoker, all underwent primary PCI). The time between the two sublingual assessments was 188±31 days. The PBR [1.96±0.22µm vs. 1.84±0.19µm]; p=0.047 and flow-adjusted PBR [1.40±0.25µm vs. 1.24±0.16µm]; p=0.045 decreased statistically significant over time. The RBC filling [71.56±4.33% vs. 74.02±3.88%]; p=0.016 and the MVHS [4.28 (interquartile range (IRQ) 3.38-4.90) vs. 5.04 (IQR 4.37-6.00)]; p=0.044 increased statistically significant over time. The PVD [500±86 x10-2µm/mm vs. 522±84x10-2µm/mm]; p=0.255 did not modify over time. Conclusion: This finding was compatible with eGC shedding and microvascular dysfunction during AMI and later reconstitution of this structure after six months.