BackgroundExertional heatstroke (EHS), a fatal illness, pronounces multiple organ dysfunction syndrome (MODS) and high mortality rate. Currently, no ideal factor prognoses EHS. Decreased monocyte human leukocyte‐DR antigen (mHLA‐DR) has been observed in critically ill individuals, particularly in those with sepsis. While most research focus on the pro‐inflammatory response exploration in EHS, there are few studies related to immunosuppression, and no report targeted on mHLA‐DR in EHS. The present study tried to explore the prognostic value of mHLA‐DR levels in EHS patients.MethodsThis was a single‐center retrospective study. Clinical data of EHS patients admitted to the intensive care unit of the General Hospital of Southern Theatre Command between January 1, 2008, and December 31, 2020, were recorded and analyzed.ResultsSeventy patients with 54 survivors and 16 nonsurvivors were ultimately enrolled. Levels of mHLA‐DR in the nonsurvivors (41.8% [38.1–68.1]%) were significantly lower than those in the survivors (83.1% [67.6–89.4]%, p < 0.001). Multivariate logistic regression indicated that mHLA‐DR (odds ratio [OR] = 0.939; 95% confidence interval [CI]: 0.892–0.988; p = 0.016) and Glasgow coma scale (GCS) scores (OR = 0.726; 95% CI: 0.591–0.892; p = 0.002) were independent risk factors related with in‐hospital mortality rate in EHS. A nomogram incorporated mHLA‐DR with GCS demonstrated excellent discrimination and calibration abilities. Compared to the traditional scoring systems, the prediction model incorporated mHLA‐DR with GCS had the highest area under the curve (0.947, 95% CI: [0.865–0.986]) and Youden index (0.8333), with sensitivity of 100% and specificity of 83.33%, and a greater clinical net benefit.ConclusionPatients with EHS were at a risk of early experiencing decreased mHLA‐DR early. A nomogram based on mHLA‐DR with GCS was developed to facilitate early identification and timely treatment of individuals with potentially poor prognosis.