Background Of the over 1 million reported cases of traumatic brain injuries reported annually in the USA, a sizeable proportion are characterized as mild. Although it is generally well-accepted that most people who suffer a mild traumatic brain injury recover within 1 to 3 months, a proportion of individuals continue to experience physiological, psychological, and emotional symptoms beyond the expected window of recovery. Depression is commonly reported following mild traumatic brain injury; however, its course, consequences, and prognostic factors remain to be well understood. Methods A systematic review will be conducted of available prospective longitudinal studies of adult mild traumatic brain injury-related depression. The aim of the systematic review is to describe the course of mild traumatic brain injury-related depression, along with its prognostic factors and health consequences. The review will comply with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. A thorough database search of peer-reviewed publications in English and French will be conducted in PubMed, Medical Literature Analysis and Retrieval System Online (MEDLINE), PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane, Embase, Scopus, Erudit, and Cairn. Independent investigators will perform study selection and data extraction. Risk of bias will be assessed using the Quality in Prognosis Studies tool, and methodological quality will be evaluated using a system inspired by the Scottish Intercollegiate Guidelines Network Methodology. Results will be presented through qualitative description and tabulation. Discussion This will be the first systematic review conducted with the aim of describing the course, prognostic factors, and health-related outcomes of depression in adults who have suffered a mild traumatic brain injury. The findings of the planned systematic review have the potential to guide research and clinical practice to effectively develop and implement evidence-based interventions aimed at preventing and alleviating mild traumatic brain injury-related depression. Systematic review registration PROSPERO CRD42015019214
