Objectives: To look into the role of serum leptin levels as a predictor of short-term outcome in acute ischemic stroke. Patient and methods: This prospective cohort study included sixty patients with their first acute ischemic stroke (19 males and 41 females). All patients underwent a full clinical evaluation as well as a thorough general and neurological examination. The NIHSS was used to assess stroke severity on admission, and the mRS was used to assess functional outcome 30 days later. Serum leptin levels and routine laboratory tests were also evaluated. All patients had neuroimaging, including CT and/or MRI brain scans. Results: it was found a statistically significant link between serum leptin levels and diabetes, hypertension, cardiac disease, and obesity. A statistically significant positive correlation was found between serum leptin levels and infarction size. There was also a statistically significant relationship between serum leptin level and stroke severity as measured by NIHSS score on admission. AIS patients with poor functional outcome as measured by mRS after 30 days of admission had highly statistically significant serum leptin levels. After adjusting for other confounding variables, a binary logistic regression analysis of neurological outcome with associated risk factors revealed that diabetes mellitus, elevated serum leptin levels, NIHSS, and mRS scores were the most significant risk factors for predicting deterioration and short-term outcome after ischemic stroke. Conclusion: Elevated serum leptin levels can be used as a significant and reliable biomarker of poor outcome after ischemic stroke, independent of other baseline variables.