ABSTRACT: Objective: Hemorrhagic shock is the leading cause of traumatic deaths; many could be potentially prevented with appropriate resuscitation. However, to initiate resuscitation, one must identify patients with hemorrhagic shock early. In this article, we determined the associations between plasma colloid osmotic pressure (COP) and clinical outcomes in severely injured trauma patients. Methods: Plasma samples were collected from 104 trauma patients upon admission to the emergency department and 10 healthy volunteers to serve as control subjects. Plasma osmolality, COP, and serum protein were measured and correlated to clinical data. Thrombelastography and impedance aggregometry were performed to assess coagulopathy. Commercial enzyme-linked immunosorbent assays were used to quantify syndecan 1. Results: Plasma COP was significantly reduced in trauma patients compared to control subjects 17.7 ± 2.6 vs. 20.7 ± 2.1 mmHg (P < 0.05) and strongly correlated to serum protein values (R2 = 0.7). We divided our cohort into low (COP ≤16.5 mmHg) and normal (COP >16.5 mmHg) subgroups, illustrating significantly higher Injury Severity Score scores in patients with low COP (21 vs. 10, P = 0.007), despite no differences in vital signs. Patients with low COP received more red blood cells, plasma, and platelets (4 vs. 0 total units, P = 0.0005) within 24 h of admission. Syndecan 1 levels were significantly higher (184 vs. 52 ng/mL, P = 0.027) in patients with low COP. Conclusions: Reduced plasma COP and serum protein in trauma patients are indicative of injury severity. In the absence of significant alterations in vital signs, plasma COP levels were associated with increased requirements for blood products and increased syndecan 1 shedding. We believe that plasma COP provides new insight in guiding resuscitation.