Emerging diseases at the human-wildlife-livestock interface are often zoonotic, hold high pandemic potential, and have high current and future risks to global health security. Development of health-based, “upstream” surveillance methods could elucidate patterns and risk factors leading to disease, and inform policy and interventions designed to maintain or improve population health. This protocol outlines a scoping review to investigate determinants of health and emerging disease in the context of the global human-wildlife-livestock interface. Four databases will be searched, including Web of ScienceTM, Medline via OVID, CAB Direct (CABI) and Agricultural and Environmental Sciences. Criteria for eligibility include full text availability in English, focus on emerging disease affecting human, livestock and wildlife at their interface, and incorporation of disease dynamics and/or changes in host, agent or environmental characteristics. Articles that focus on in vitro work or that are not peer-reviewed primary literature (including scoping or systematic reviews) will be excluded. Results will be uploaded to Covidence, de-duplicated, then screened by two reviewers. Data charting will include classification and name of disease or topic, classification of livestock and wildlife species, geographic location, risk factors or determinants of health/disease, study design, study focus, and author-reported study limitations and calls to action. These findings will improve understanding of health maintenance at the intersection of wild and domestic species, and will provide sentinel factors which might be used to develop health-based surveillance strategies.