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Introduction: The prevalence and incidence of sport-related concussion have continued to increase over the past decade, and researchers from various backgrounds strive for evidenced-based clinical assessment and management. When diagnosing and managing a concussion, a battery of tests from several domains (e.g., symptom reporting, neurocognitive, physiology) must be used. In this study, we propose and develop an objective, evidence-based protocol to assess the pathophysiology of the brain by using non-invasive methods. Methods: Contact sport athletes (n = 300) will be assessed at the beginning of the season in a healthy state to establish baseline values, and then prospectively followed if a mild traumatic brain injury (mTBI) occurs on approximately days 1–2, 3–5, 7–10, 21, 30, and subsequently thereafter, depending on the severity of injury. The protocol includes spontaneous measurements at rest, during head postural change, controlled breathing maneuvers for cerebrovascular reactivity, a neurovascular coupling stimuli, and a baroreflex/autoregulation maneuver. Physiological data collection will include cerebral blood flow velocity, cerebral oxygenation, respiratory gases for end-tidal oxygen and carbon dioxide, finger photoplethysmography for blood pressure, seismocardiography for cardiac mechanics, and electrocardiography. Conclusion, Limitations, and Ethics: The protocol will provide an objective, physiological evidence-based approach in an attempt to better diagnose concussion to aid in return-to-play or -learn. Ethics approval has been granted by the University Research Ethics Board.