BACKGROUND: While overall physical activity is clearly associated with a better short-term and long-term health, prolonged strenuous physical activity may result in a rise in acute levels of blood-biomarkers used in clinical practice for diagnosis of various conditions or diseases. In this study, we explored the acute effects of a full Ironman-distance triathlon on biomarkers related to heart-, liver-, kidney- and skeletal muscle damage immediately post-race and after one week's rest. We also examined if sex, age, finishing time and body composition influenced the post-race values of the biomarkers. METHODS: A sample of 30 subjects was recruited (50% women) to the study. The subjects were evaluated for body composition and blood samples were taken at three occasions, before the race (T1), immediately after (T2) and one week after the race (T3). Linear regression models were fitted to analyse the independent contribution of sex and finishing time controlled for weight, body fat percentage and age, on the biomarkers at the termination of the race (T2). Linear mixed models were fitted to examine if the biomarkers differed between the sexes over time (T1-T3). RESULTS: Being male was a significant predictor of higher post-race (T2) levels of myoglobin, CK, and creatinine levels and body weight was negatively associated with myoglobin. In general, the models were unable to explain the variation of the dependent variables. In the linear mixed models, an interaction between time (T1-T3) and sex was seen for myoglobin and creatinine, in which women had a less pronounced response to the race. CONCLUSION: Overall women appear to tolerate the effects of prolonged strenuous physical activity better than men as illustrated by their lower values of the biomarkers both post-race as well as during recovery.