Malaria is caused by Plasmodium infection and remains a se rious public health problem worldwide, despite control ef forts. Malaria can progress to severe forms, affecting multi ple organs, including the brain causing cerebral malaria (CM). CM is the most severe neurological complication of malaria, and cognitive and behavior deficits are commonly reported in surviving patients. The number of deaths from malaria has been reducing in recent years, and as a conse quence, neurological sequelae have been more evident. Neurological damage in malaria might be related to the neu roinflammation, characterized by glia cell activation, neuro nal apoptosis and changes in the blood-brain barrier (BBB) integrity. The neurovascular unit (NVU) is responsible for maintaining the homeostasis of the BBB. Endothelial and pericytes cells in the cerebral microvasculature and neural cells, as astrocytes, neurons, and microglia, compose the NVU. The NVU can be disturbed by parasite metabolic prod ucts, such as heme and hemozoin, or cytokines that can promote activation of endothelial and glial cells and lead to in creased BBB permeability and subsequently neurodegener ation. In this review, we will approach the main changes that happen in the cells of the NVU due to neuroinflammation caused by malaria infection, and elucidate how the systemic pathophysiology is involved in the onset and progression of CM.