Septic associated encephalopathy (SAE) is simply define as an encephalopathy incidence that occurs in sepsis patients. Ironically this entity can increases the mortality rate. Importantly, the clinical presentations of this entity is vary ranging from malaise to coma condition. The central nervous system is susceptible to damage that caused by systemic inflammation including sepsis with complex pathophysiologies such as endothelial dysfunction, neurotransmitter imbalance, oxidative stress, mitochondrial dysfunction and apoptosis. In general, current management of SAE is similar with the management of sepsis incidence which includes infections management, maintaining tissue perfusion and symptomatic therapy to treat delirium and convulsions that may occur. Also, several studies continue to be developed including the use of corticosteroids, magnesium, antioxidants, and immunoglobulin. Early identification and appropriate initial handling significantly affect the output of the SAE patients.