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To investigate changes in serum concentrations of the biochemical markers of brain damage S-100B and neuron-specific enolase (NSE) in ice hockey and basketball players during games.Descriptive clinical research.Competitive games of the Swedish Elite Ice Hockey League and the Swedish Elite Basketball League.Twenty-six male ice hockey players (from two teams) and 18 basketball players (from two teams).None.S-100B and NSE were analyzed using two-site immunoluminometric assays. The numbers of acceleration/deceleration events were assessed from videotape recordings of the games. Head trauma–related symptoms were monitored 24 hours after the game using the Rivermead Post Concussion Symptoms Questionnaire.Changes in serum concentrations of S-100B (postgame − pregame values) were statistically significant after both games (ice hockey, 0.072 ± 0.108 μg/L, P = 0.00004; basketball, 0.076 ± 0.091 μg/L, P = 0.001). In basketball, there was a significant correlation between the change in S-100B (postgame − pregame values) and jumps, which were the most frequent acceleration/deceleration (r = 0.706, P = 0.002). For NSE, no statistically significant change in serum concentration was found in either game. For one ice hockey player who experienced concussion during play, S-100B was increased more than for the other players.S-100B was released into the blood of the players as a consequence of game-related activities and events. Analysis of the biochemical brain damage markers (in particular S-100B) seems to have the potential to become a valuable additional tool for assessment of the degree of brain tissue damage in sport-related head trauma and probably for decision making about returning to play.