Abstract: Acute ischemic stroke is a sudden neurological event caused by brain ischemia. Patients with large vessel occlusion are at high risk of developing significant cerebral edema, which can lead to rapid neurological decline. The optimal timing for decompressive hemicraniectomy to prevent further brain damage is still uncertain. This study aimed to identify potential predictors of severe brain edema. The data indicate that specific cytokines may help identify patients with a higher risk of developing life-threatening brain swelling in the early phase post-stroke. The association between a positive biomarker and the outcome was calculated, and three biomarkers—S100B protein, MMP-9, and IL-10—were found to be significantly associated with malignant edema. A model was derived for early predicting malignant cerebral edema, including S100B protein and IL-1 beta. These findings suggest that molecular biomarkers related to the ischemic cascade may be a helpful way of predicting the development of malignant cerebral edema in ischemic stroke patients, potentially widening the time window for intervention and assisting in decision-making. In conclusion, this study provides insights into the molecular mechanisms of severe brain edema and highlights the potential use of biomarkers in predicting the course of ischemic stroke Ver menos