Previous data have revealed an association between eosinopenia and mortality of acute ischemic stroke. However, the relationship of eosinopenia with infarct volume, infection rate, and poor outcome of acute ischemic stroke is still unknown. The retrospective study in-cluded 421 patients (273 males, 65%; mean age, 68.0 ± 13.0 years) with first acute ischemic stroke who were hospitalized in the Second Afliated Hospital of Soochow University, China, from January 2017 to February 2018. Laboratory data, neuroimaging results, and mod-ified Rankin Scale scores were collected. Patients were divided into four groups according to their eosinophil percentage level (＜ 0.4%, 0.4-1.1%, 1.1-2.3%, ≥ 2.3%). Spearman’s correlation analysis showed that the percentage of eosinophils was negatively correlated with infarct volume (rs = -0.514, P ＜ 0.001). Receiver operating characteristic analysis demonstrated that eosinopenia predicted a large infarct volume more accurately than neutrophilia; the area under curve was 0.906 and 0.876, respectively; a large infarct was considered as that with a diameter larger than 3 cm and involving more than two major arterial blood supply areas. Logistic regression analysis revealed that eosinophil percentage was an independent risk factor for acute ischemic stroke (P = 0.002). Moreover, eosinophil percentage was signifi-cantly associated with large infarct volume, high infection rate (pulmonary and urinary tract infections), and poor outcome (modified Rankin Scale score ＞ 3) after adjusting for potential confounding factors (P-trend ＜ 0.001). These findings suggest that eosinopenia has the potential to predict the severity of acute ischemic stroke. This study was approved by the Ethics Committee of the Second Afliated Hospital of Soochow University, China (approval number: K10) on November 10, 2015.