Biomarkers that reflect brain damage or predict functional outcomes may aid in guiding personalized stroke treatments. Serum neurofilament light chain (sNfL) emerges as a promising candidate for fulfilling this role. This prospective, observational cohort investigation included 319 acute ischemic stroke (IS) patients. The endpoints were the incidence of early neurological deterioration (END, an elevation of two or more points in the National Institute of Health stroke scale score within a week of hospitalization compared with the baseline) and functional outcome at 3 months (an mRS score of >2 at 3 months was categorized as an unfavorable/poor functional outcome). The association of sNfL, which was assessed within 24 h of admission, with END and unfavorable functional outcomes at follow-up was assessed via multivariate logistic regression, whereas the predictive value of sNfL for unfavorable functional outcomes and END was elucidated by the receiver operating characteristic curve (ROC). Of 319 IS individuals, 89 (27.90%) suffered from END. sNfL not only reflects the severity of stroke measured by NIHSS score (p < 0.05) but also closely related to the severity of age-related white matter changes. Higher initial NIHSS score, severe white matter lesions, diabetes mellitus, and upregulated sNfL were significant predictors of END. Similarly, the multivariate logistic regression analysis results showed that elevated sNfL, a higher baseline NIHSS score, and severe white matter lesions were substantially linked with unfavorable outcomes for 3 months. Similarly, sNfL was valuable for the prediction of the 3 months of poor outcome (95%CI, 0.504-0.642, p = 0.044). Kaplan-Meier analysis shows that patients with elevated sNfL levels are more likely to reach combined cerebrovascular endpoints (log-rank test p < 0.05). This investigation suggests that sNfL can serve as a valuable biomarker for predicting END and 3-month poor functional outcomes after an IS and has the potential to forecast long-term cardiovascular outcomes.