Shahim and colleagues determine whether sports-related concussion is associated with elevated levels of blood biochemical markers of injury to the central nervous system and assess whether plasma levels of these biomarkers predict return to play in professional ice hockey players with sports-related concussion. Total tau, S-100 calcium-binding protein B, and neuron-specific enolase concentrations in plasma and serum were measured. Sports-related concussion in professional ice hockey players is associated with acute axonal and astroglial injury. This can be monitored using blood biomarkers, which may be developed into clinical tools to guide sport physicians in the medical counseling of athletes in return-to-play decisions. Gatson and Diaz-Arrastia provide commentary in an accompanying editorial.