Objective Neuroglobin (Ngb) has been described as a neuroprotective agent in cerebral ischemia, which has a high affinity for oxygen and helps to prevent hypoxic-ischemic brain damage, and to affect the outcomes after acute ischemic stroke (AIS). In this study, the changes of serum Ngb level after AIS were investigated and the relationship of Ngb and stroke severity and prognosis were evaluated.Methods We prospectively measured the serum levels of Ngb in AIS patients at different time points (within 72 h and on day 14 (D14) after onset of cerebral infarction) and in control subjects. Serum Ngb levels were compared between the AIS patients and controls. The serum Ngb levels in the AIS patients with and without diabetes mellitus (DM) were also compared. Correlations between Ngb level and infarct size and that between Ngb level and National Institutes of Health Stroke Scale (NIHSS) score of the patients were analyzed. Receiver operating characteristic (ROC) curve was used to appraise their value in predicting the outcome at day 90 after AIS, which was evaluated using the modified Rankin Scale (mRS).Results Serum Ngb levels in patients were 105.7 (88.3, 123.1) μg/L within 72 h and 72.8 (58.7, 86.9) μg/L on D14 after cerebral infarction, respectively. Serum Ngb level in control group was 58.2 (35.0, 81.6) μg/L. Serum Ngb level within 72 h after AIS increased significantly compared with that in the control group (P<0.05). Serum Ngb levels of AIS patients with or without DM showed no significant difference within 72 h and on D14 after AIS (P>0.05). Serum Ngb level within 72 h was significantly correlated with NIHSS score (Spearman correlation coefficient=0.232, P=0.038). Serum Ngb levels had no significant difference in patients with large infarction than in those with small or moderate infarction at each time point (P>0.05). ROC curve analysis suggested that the serum Ngb level had a significantly good predictive power for outcomes.Conclusion The results indicated that serum Ngb level increased within 72 h after AIS, which is independent of comorbidity with diabetes. Serum Ngb level within 72 h was significantly correlated with NIHSS score, and Ngb might have the potential to be a predictor of stroke severity and prognosis.