INTRODUCTION: Acute traumatic coagulopathy (ATC) is an endogenous impairment in hemostasis that often contributes to early mortality after trauma. Endothelial glycocalyx damage is associated with trauma-induced coagulation abnormalities; however, the specific relationship between hyaluronan (HA), a key glycocalyx constituent, and ATC has not been evaluated. METHODS: We performed a secondary analysis of prospectively collected data from a recent study in which trauma patients (>18 years) admitted to our Level I trauma center with an ABC Score≥2 were enrolled. Partial thromboplastin time (PTT), international normalized ratio (INR), and thromboelastography (TEG) parameters were recorded at arrival. Injury characteristics and clinical outcomes were obtained. Plasma HA levels were measured in healthy controls (HC) and in trauma subjects at arrival (t = 0 h) and 12, 24, and 48 h. ATC was defined as admission INR>1.2 or PTT≥36.5 s. Comparisons of HA levels were assessed, and Spearman's correlations were performed between 0 h and 24 h HA levels, coagulation measures and clinical outcomes. P values < 0.05 were considered significant. RESULTS: Forty-eight trauma patients and 22 controls were enrolled for study. Sixteen trauma subjects were coagulopathic at admission. HA levels in subjects with ATC were higher than non-coagulopathic subjects at all time points and elevated above HC levels at 24 and 48 h. At arrival, HA levels correlated with TEG R-time, PTT, and INR. HA levels at 24 h correlated with increased transfusion requirements and intensive care unit and hospital lengths of stay. CONCLUSION: Shed HA is associated with early coagulation abnormalities in trauma patients, which may contribute to worse outcomes. These findings highlight the need for additional studies to evaluate the mechanistic role of HA in ATC.