Introduction Reports on the association between comorbidity and functional status and risk of death in patients with traumatic brain injury (TBI) have been inconsistent; it is currently unknown which additional clinical entities (comorbidities) have an adverse influence on the evolution of outcomes across the lifespan of men and women with TBI. The current protocol outlines a strategy for a systematic review of the current evidence examining the impact of comorbidity on functional status and early-term and late-term mortality, taking into account known risk factors of these adverse outcomes (ie, demographic (age and sex) and injury-related characteristics).

Methods and analysis A comprehensive search strategy for TBI prognosis, functional (cognitive and physical) status and mortality studies has been developed in collaboration with a medical information specialist of the large rehabilitation teaching hospital. All peer-reviewed English language studies with longitudinal design in adults with TBI of any severity, published from May 1997 to April 2017, found through Medline, Central, Embase, Scopus, PsycINFO and bibliographies of identified articles, will be considered eligible. Study quality will be assessed using published guidelines.

Ethics and dissemination The authors will publish findings from this review in a peer-reviewed scientific journal(s) and present the results at national and international conferences. This work aims to understand how comorbidity may contribute to adverse outcomes in TBI, to inform risk stratification of patients and guide the management of brain injury acutely and at the chronic stages postinjury on a population level.

PROSPERO registration number CRD42017070033.