Background Orosomucoid (ORM) is a positive acute phase protein verified to be upregulated in various forms of exercise-induced fatigued (EIF) rodents. However, its association with EIF among human beings remained unknown. This study aimed to explore the association between serum ORM and EIF triggered by military basic combat training (BCT). Methods The degree of EIF were measured by Borg’s Rating of Perceived Exertion Scale (Borg-RPE-Scale®) as RPE score after BCT. Fifty-three male recruits were classified into three groups according to the RPE score: (1) group 1 (slight fatigue group): RPE score after BCT < 13; (2) group 2 (moderate fatigue group): RPE score after BCT = 13 or 14; (3) group 3 (severe fatigue group): RPE score after BCT > 14. The levels of blood ORM, lactate (LAC), cortisol and C-reactive protein (CRP) were determined before and after BCT. The diagnostic value of ORM was evaluated by receiver operating characteristic (ROC) curve analysis and logistic regression. Results After BCT, the level of LAC, CRP, and cortisol increased among all groups, but the changes had no significant between-group difference (all p > 0.05). The level of ORM had a specific significant increase in group 3 (p = 0.039), and the changes of ORM (ΔORM) had significant difference among groups (p = 0.033). ROC curve analysis showed that the estimated area under ROC curve for ΔORM was 0.724 (p = 0.009) with the recommended optimal cut-off value as 0.2565 mg/mL. Logistic analysis showed that recruits with ΔORM ≥ 0.2565 mg/mL had higher odds for suffering from severe EIF, 5.625 times (95% CI 1.542–20.523, p = 0.009) as large as those with ΔORM < 0.2565 mg/mL. Conclusion ORM might be a promising biomarker of severe EIF triggered by BCT among male recruits. Its potential optimal cut-off value regarding ΔORM was recommended to be 0.2565 mg/mL.
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