Background: In the early period of spontaneous circulation (ROSC), the body may show severe immunosuppression and excessive activation of inflammatory response, This is very similar to sepsis in many ways. Objective: The aim of this study is to observe changes of the early expression of monocyte human leukocyte antigen DR in patients with cardiac arrest, so as to explore the clinical significance of the related immune assessment and prognosis prediction. Methods: A total of 43 patients with cardiac arrest who have been treated in the emergency department of Beijing Chaoyang Hospital from January 2015 to February 2018 are selected. By taking the survival rate on the 28th day of hospitalization as the end of observation, the patients are divided into the survival group and the death group. Changes of APACHE-II scores and monocyte human leukocyte antigen DR levels on the first, second, and third day after admission are analyzed. Results: On the first, second, and third day after onset, cardiac arrest patients show significantly decreased levels of monocyte human leukocyte antigen DR which are obviously lower in the death group than in the survival group. In addition, human leukocyte antigen DR levels were significantly negatively correlated with APACHE-II scores. Conclusion: The expression of monocyte human leukocyte antigen DR is proven to be an ideal indicator to evaluate the immune function and prognosis of cardiac arrest patients. A constantly low expression of human leukocyte antigen DR indicates impaired immune function and increased mortality of patients.