INTRODUCTION: It can be challenging at times to clinically differentiate between acute seizure and acute stroke. This study aimed to compare the computed tomography perfusion (CTP) changes in patients presenting with acute seizures of different etiologies to those with acute cortical stroke. METHODS: We conducted a single-center cross-sectional case-control study on the CTP changes of 31 patients presenting with acute seizures of different etiologies, and compared them with 31 patients of acute cortical stroke patients (n = 31) as the control. RESULTS: 58.1% had increased time to peak (TTP) in the seizure group. None of the patients with acute stroke had reduced TTP compared to 25.8% in the seizure group. The majority of patients in the seizure group had normal to reduced relative cerebral blood flow (rCBF) (38.7% and 35.5%, respectively). 35.5% and 38.7% of the patients presenting with acute seizures had normal and reduced relative cerebral blood volume (rCBV), respectively. The association between the perfusion parameters and etiology of seizures, presence of underlying epilepsy, or presence of postictal neurological deficits was not statistically significant. The seizure group had cortical ribbon (51.6%), holo-hemispheric (32.3%), multi-lobar (9.7%), and normal (6.5%) CT perfusion patterns. In conclusion, our study shows that the majority of the patients of the acute seizure group had normal to hypoperfusion patterns. Seizure-related perfusion changes did not conform to expected vascular territories, and cortical ribbon pattern was found to be predominant in our study. SIGNIFICANCE: There is cerebral hypoperfusion or normal perfusion in most patients presenting with acute seizures. Seizure-related perfusion changes are not limited to arterial vascular territories.