Background: Exertional heat stroke (EHS) is a life-threatening illness that can lead to multiple organ damage in the early stage. Objective: This study aimed to investigate the relationship between 24-hour indicators and mortality in patients with EHS. Methods: The records of EHS patients hospitalized were collected and divided into the death group and the survival group. We then analyzed the demographic characteristics and APACHE II scores and laboratory results of the participants in the blood within the first 24 h after hospitalization, and assessed whether these candidate indicators differed between the death group and the survival group. Cox regression analysis of the survival data was performed to explore the relationship between early indicators and prognosis. Results: The levels of plasma PT, APTT, TT, and INR were significantly higher in the death group than in the survival group. The blood PLT count and the levels of PTA and Fb were significantly lower in the death group than in the survival group, while the levels of BU, SCr, ALT, AST, TBil, and DBil were significantly higher in the death group than in the survival group. Furthermore, the levels of Mb, LDH, TNI, and NT-proBNP were significantly higher in the death group than in the survival group, while there was no significant difference in CK levels between the two groups. Conclusion: Patients with EHS often had multiple organ injuries in the early stage (within 24 h), while those cases in the death group were more severe.