OBJECTIVE: To establish sex- and sport-specific reference intervals (RIs) for the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) in athletes. METHODS: A retrospective study analyzed 13,647 entries from elite athletes (2018-2024), categorized by sex and six sport types. RIs were developed using a training set (9555 entries) and validated with a separate set (4092 entries). The RIs were defined using the 2.5th and 97.5th percentiles of the distribution. RESULTS: Females had higher RIs compared to males: NLR (females: 1.53 [0.74, 3.25]
males: 1.36 [0.70, 2.89]), PLR (females: 124 [69, 223]
males: 111 [65, 188]), and SII (females: 347 [146, 804]
males: 298 [139, 684]) (p <
0.001). Sport type influenced RIs, with significant differences noted across categories (p <
0.001). Validation showed an outlier rate below 10% across all groups, confirming robustness. CONCLUSION: These sex- and sport-specific RIs enhance the precision of health assessments, supporting early detection of overtraining and inflammation in athletes. Future studies should expand to diverse populations and consider factors like age and training cycles.