Mounting evidence suggests that ischemic stroke (IS) is associated with Alzheimer's disease (AD). IS and vascular risk factors increase the risk for AD. However, whether AD pathologies exist in IS and the effects of these pathologies on stroke remain unknown. In the present study, we aimed to investigate the alterations of serum Aβ after acute IS (AIS), and its correlations with the neurological deficits, infarction volume, and site after stroke. AIS patients (n = 35) were recruited within 24 h of symptom onset. Age- and gender-matched AD patients (n = 48) and cognitively normal controls (NC, n = 37) were also enrolled. Serum Aβ40 and Aβ42 and the National Institute of Health Stroke Scale Score (NIHSS) were measured on day 1, 3, and 7 after stroke onset. We found that serum Aβ40 and Aβ42 levels were increased at day 1 and reached peak levels at day 3, and decreased to pre-stroke levels at day 7. Serum Aβ40 levels at day 1 were correlated with the NIHSS scores and infarction volume of AIS patients. Serum Aβ42 levels at day 1 were significantly higher in IS patients with dominant gray matter infarction. Serum Aβ40 levels at day 1 were predictive for NIHSS at day 7. Our results indicate that AIS can induce the generation of Aβ in the brain, which may in turn be involved in the pathogenesis of neurological deficits after stroke. Serum Aβ might be predictive for the short-term neurological deficits after AIS.