IGF-I is a biomarker that may have greater utility than other conventional biomarkers in assessing nutritional, health, and fitness status. We hypothesized the IGF-I system would directionally track a short-term energy deficit and would be more related to changes in body composition than other nutritional biomarkers. 35 healthy men (24±0.3 y) underwent 8 days of exercise and energy imbalance. Total and free IGF-I, IGFBP-1, - 2 and -3, the acid labile subunit (ALS), transferrin, ferritin, retinol binding protein (RBP), prealbumin, testosterone, T3, T4, leptin and changes in body composition were measured. Repeated measures ANOVA, correlation analysis and receiver operator characteristic (ROC) curves were used for statistical analyses (p 0 .05). Results: Body mass (-3.8 %), fat-free mass (-2.2%), and fat mass (- 12.9%) all decreased. Total and free IGF-I, IGFBP-3 and the ALS and prealbumin, but not transferrin, RBP and ferritin directionally tracked the energy deficit and losses in body composition. The correlation (r = 0.43) between changes in free IGF-I and body and fat-free mass was the only significant association observed. ROC curve analysis revealed that a baseline value < 1.67 for the molar volume ratio of IGF-I/ALS had an AUC of 0.745 and was a significant discriminator for those subjects losing >5 % body mass. Conclusions: IGF-I is an important adjunct in the overall assessment of adaptation to stress imposed by pysical activity superimposed upon energy and sleep restriction and is more closely associated with losses in body mass and fat-free mass than other conventional nutritional biomarkers.