Background: Cerebral malaria (CM) is the most severe complication of Plasmodium falciparum infection, associated with cerebral edema, seizures, and high mortality. Optimizing cerebral hemodynamics is essential to improve outcomes.

Case Report: We describe a 28-year-old man returning from Côte d’Ivoire who presented with a 4% parasitemia. Rapid deterioration required intensive care admission, mechanical ventilation, and intravenous artesunate. Multimodal neuromonitoring included continuous electroencephalography, intracranial pressure (ICP) monitoring, and cerebral autoregulation assessment using the long-pressure reactivity index (L-PRx). Despite parasite clearance, cerebral edema developed with radiological signs of intracranial hypertension and ischemic lesions on magnetic resonance imaging. L-PRx demonstrated impaired cerebral autoregulation, whereas ICP remained within noncritical ranges. Continuous electroencephalography excluded epileptiform activity. Gradual neurological improvement allowed extubation after 14 days and hospital discharge after 65 days.

Conclusion: This is the first report demonstrating cerebral autoregulatory dysfunction in CM using L-PRx and supports multimodal neuromonitoring to guide individualized hemodynamic strategies to prevent secondary brain injury.