Heatstroke is a medical emergency that causes multi-organ injury and death without intervention, but limited data are available on the illness scores in predicting the outcomes of exertional heat stroke (EHS) with rhabdomyolysis (RM). The aim of our study was to investigate the Sequential Organ Failure Assessment (SOFA) score in predicting mortality of patients with RM after EHS. A retrospective cohort study was performed, which included all patients with EHS admitted into the intensive care unit (ICU) of General Hospital of Southern Theater Command of Peoples Liberation Army from January 2008 to June 2019. RM was defined as creatine kinase (CK) > 1,000 U/L. Data, including the baseline data at admission, vital organ function indicators, and 90-day mortality, were reviewed. A total of 176 patients were enrolled; among them, 85 (48.3%) had RM. Patients with RM had a significantly higher SOFA score (4.0 vs. 3.0, = 0.021), higher occurrence rates of disseminated intravascular coagulation (DIC) (53.1 vs. 18.3%, < 0.001) and acute liver injury (ALI) (21.4 vs. 5.5%, = 0.002) than patients with non-RM. RM was positively correlated with ALI and DIC, and the correlation coefficients were 0.236 and 0.365, respectively (both -values <0.01). Multivariate logistics analysis showed that the SOFA score [odds ratio (OR) 1.7, 95% CI 1.1-2.6, = 0.024] was the risk factor for 90-day mortality in patients with RM after EHS, with the area under the curve (AUC) 0.958 (95% CI 0.908-1.000, < 0.001) and the optimal cutoff 7.5 points. Patients with RM after EHS have severe clinical conditions, which are often accompanied by DIC or ALI. The SOFA score could predict the prognosis of patients with RM with EHS. Early treatment strategies based on decreasing the SOFA score at admission may be pivotal to reduce the 90-day mortality of patients with EHS.