Abstract: BACKGROUND: The complex neurobiology of post-traumatic stress disorder (PTSD) calls for the characterization of specific disruptions in brain functions that require targeted treatment. One such alteration could be an overactive locus coeruleus-norepinephrine (LC-NE) system, which may be linked to hyperarousal symptoms, a characteristic and burdensome aspect of the disorder. METHODS: Study participants were Canadian Armed Forces veterans with PTSD related to deployment to combat zones (n=34) and age-and-sex matched healthy controls (n=32). Clinical measures included the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and neuroimaging measures included a neuromelanin-sensitive MRI scan to measure LC signal. Robust linear regression analyses related LC signal to clinical measures. RESULTS: Compared to controls, LC signal was significantly elevated in the PTSD group (t(62)=2.64, p=0.010) and this group difference was most pronounced in the caudal LC (t(56)=2.70, Cohen's d=0.72). Caudal LC signal also positively correlated to the severity of CAPS-5 hyperarousal symptoms in the PTSD group (t(26)=2.16, p=0.040). CONCLUSION: These findings are consistent with a growing body of evidence indicative of elevated LC-NE system function in PTSD. Furthermore, they indicate the promise of NM-MRI as a non-invasive method to probe the LC-NE system that has the potential to support subtyping and treatment of PTSD or other neuropsychiatric conditions.