Background: There is paucity of literature on the prognostic value of tissue oxygen saturation (StO(2)) and regional cerebral oxygen saturation (rSO(2)) in neurological patients with sepsis. In this preliminary study, we investigated the prognostic value of StO(2) and rSO(2) in a group of neurological patients and correlated StO(2) and rSO(2) with hemodynamic and metabolic parameters. Materials and Methods: This preliminary, prospective observational study was conducted in 45 adult neurological patients admitted to intensive care unit. Once a diagnosis of sepsis or septic shock was established, parameters of oxygenation (StO(2), rSO(2), central venous oxygen saturation [ScvO(2)]), serum lactate, illness severity scores (Acute Physiology and Chronic Health Evaluation score, Sequential Organ Failure Assessment score, Glasgow Coma Scale) were recorded at 0, 6, 12, 24, 36, and 48 hours, and once daily thereafter. Outcomes were in-hospital mortality attributable to sepsis and the Glasgow outcome score at hospital discharge. Results: There was a moderately positive correlation between StO(2) and rSO(2) at baseline (r=0.599; P=0.001). StO(2), illness severity scores and serum lactate, but not rSO(2), were significantly different between survivors (n=29) and nonsurvivors (n=16) at baseline and during the first 48 hours. An rSO(2) of 62.5% had a sensitivity of 83% and specificity of 67% to differentiate survivors and nonsurvivors of septic shock at 48 hours. StO(2) had a higher correlation with ScvO(2) and serum lactate than rSO(2). Conclusions: StO(2) prognosticates survival and favorable/unfavorable outcomes in neurological patients with sepsis. The role of rSO(2) in predicting survival in milder form of sepsis is doubtful.