Several studies have demonstrated that anemia was associated with cognitive impairment. The aim of this study was to explore the relationship between hemoglobin and cognitive impairment in patient with acute ischemic stroke. In total, 326 patients with acute ischemic stroke were followed up for 1 month. The main outcome was the incidence and severity of poststroke cognitive impairment (PSCI) assessed by Mini-Mental State Examination (MMSE). The impact of hemoglobin levels and anemia on PSCI was assessed by multiple regression models controlling for potential confounders. During the 1-month follow-up, 193 (59.2%) patients developed PSCI. Anemia was independently associated with PSCI (OR = 3.637; 95% CI, 1.216-10.881; P = .021) after adjusting for demographics, vascular risk factors, stroke severity, and functional outcome. When the hemoglobin levels stratified into tertiles, higher hemoglobin levels were associated with better cognitive function. This result was however not significant after adjusting for the same confounders above. Low hemoglobin levels are associated with an increased risk of PSCI. Targeted interventions in this population may reduce the incidence of PSCI and require further evaluation. © 2020 John Wiley & Sons Ltd.