ObjectiveTo evaluate whether participating in physical contact sports is associated with a release of neurofilaments and whether such release is related to future clinical neurological and/or psychiatric impairment.MethodsWe performed a systematic review of the PubMed, MEDLINE and Cochrane Library databases using a combination of the search terms neurofilament(s)/intermediate filament and sport(s)/athletes. Original studies, written in English, reporting on neurofilaments in cerebrospinal fluid and/or serum/plasma of contact sport athletes were included. This review was conducted following the Preferred Reporting Items for Systematic Review and Analyses guidelines.ResultsEighteen studies in eight different contact sports (i.e. boxing, American football, ice hockey, soccer, mixed martial arts, lacrosse, rugby and wrestling) matched our criteria. Elevated light chain neurofilament (NfL) levels were described in 13/18 cohorts. Most compelling evidence was present in boxing and American football, where exposure-related increases were appreciable at the intra-individual level (up to 4.1- and 2.0-fold, respectively) in well-defined groups. Differences in exposure severity (including previous cumulative effects), sampling/measurement time points (with regard to expected peak values) and definitions of the baseline setting are considered as main contributors to the variability in findings. No studies were encountered that have investigated the relationship with the targeted clinical endpoints; therefore no NfL cut-offs exist that are associated with a poor outcome.ConclusionNfL release can be seen, as a potential marker of neuronal brain damage, in participants of physical contact sports, particularly boxing and American football. The exact significance regarding the risk for future clinical impairment remains to be elucidated.