Purpose Over 1 in 5 people who are severely injured will develop PTSD and depression. However, it is not well understood in the immediate aftermath of injury who is at risk for this chronic pathology. The purpose of the present study was to evaluate the role of early (within 2 days) endocannabinoid and cortisol functioning in posttraumatic stress disorder and depression 6 months following traumatic injury. Methods 31 participants who had experienced a traumatic injury requiring hospitalization underwent a blood draw early after trauma, as well as an assessment of PTSD and peritraumatic emotion regulation. At 6-months post-injury subject PTSD and depression symptoms were assessed, and another blood draw was completed. Pearson correlation analyses were used to evaluate the relationship between cortisol, 2-AG, and AEA and the symptom clusters of PTSD (avoidance, intrusions, hyperarousal, negative alterations in mood and cognitions), depression, stress, anxiety, and emotion regulation. These are preliminary analyses of a large scale study evaluating the endocannabinoid system as a marker for PTSD. Results Significant correlations were found between baseline 2-AG, AEA, and cortisol and peritraumatic emotionality and previous trauma history, as well as 6 month scores of hyperarousal, negative alterations in mood, and stress scores. Summary These preliminary data suggest a relationship between cortisol and the endocannabinoid system early after trauma that may play a role in emotional reactivity and psychological distress outcomes.