Shedding of syndecan-1 from the endothelial glycocalyx layer (EGL), referred to as endotheliopathy of trauma (EoT), is associated with poorer outcomes. This study aims to determine if EoT is also present in the burn population. We enrolled 458 burn and non-burn trauma patients at a Level 1 trauma center and defined EoT by a syndecan-1 level of ≥40 ng/mL. Sixty-eight of the enrolled patients had burns with a median TBSA of 19%, with 27.9% also suffering inhalational injury (II). Mortality was similar between the burn and non-burn group, also for patients with EoT. The incidence of II was significantly greater in the EoT+ burn group compared to the EoT- group (p = 0.038). Patients with II received significantly larger amounts of i.v. fluids (p = 0.001). The incidence of EoT was significantly different between the II-groups, as was mortality (pEoT = 0.038, pmortality < 0.001). EoT is attributed to the shock rather than the mechanism of trauma and may in burns be associated to II rather than TBSA. Patients with burns and II had worse outcomes and higher mortality compared to patients with burns alone. Burn injury induces EGL shedding similar to that in non-burn patients with EoT, and results in similar higher rate of mortality.