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Emerging evidence suggests that repeated blast exposure (RBE) is associated with brain injury in military personnel. United States (U.S.) Special Operations Forces (SOF) personnel experience high rates of blast exposure during training and combat, but the effects of low-level RBE on brain structure and function in SOF have not been comprehensively characterized. Further, the pathophysiological link between RBE-related brain injuries and cognitive, behavioral, and physical symptoms has not been fully elucidated. We present a protocol for an observational pilot study, Long-Term Effects of Repeated Blast Exposure in U.S. SOF Personnel (ReBlast). In this exploratory study, 30 active-duty SOF personnel with RBE will participate in a comprehensive evaluation of: 1) brain network structure and function using Connectome magnetic resonance imaging (MRI) and 7 Tesla MRI; 2) neuroinflammation and tau deposition using positron emission tomography; 3) blood proteomics and metabolomics; 4) behavioral and physical symptoms using self-report measures; and 5) cognition using a battery of conventional and digitized assessments designed to detect subtle deficits in otherwise high-performing individuals. We will identify clinical, neuroimaging, and blood-based phenotypes that are associated with level of RBE, as measured by the Generalized Blast Exposure Value. Candidate biomarkers of RBE-related brain injury will inform the design of a subsequent study that will test a diagnostic assessment battery for detecting RBE-related brain injury. Ultimately, we anticipate that the ReBlast study will facilitate the development of interventions to optimize the brain health, quality of life, and battle readiness of U.S. SOF personnel.