This study used spatially resolved transcranial near-infrared spectroscopy (NIRS) to compare brain tissue oxygenation in sickle cell disease (SCD) patients with that of healthy children. In addition, NIRS was used to measure the dynamic response of cerebral oxygen balance to erythrocytapheresis. Transcranial NIRS measurements were obtained from 25 children with SCD who were not receiving transfusion or hydroxyurea therapy (NT-SCD). These patients were divided into two subgroups, those with mild (n = 10) or severe (n = 15) SCD symptoms. In addition, NIRS measurements were performed in 16 SCD patients with severe disease maintained on long-term erythrocytapheresis (T-SCD) and in 35 control children. The lowest mean brain tissue oxygen saturation occurred in the NT-SCD subgroup with severe symptoms (48 +/- 9%; P < 0.001 vs. control). NT-SCD patients with mild symptoms had higher saturation (62 +/- 8%; P < 0.001 vs. control), while the highest appeared in the control group (72 +/- 7%). In T-SCD patients, however, brain tissue oxygen saturations were higher than severely symptomatic NT-SCD children and similar to mildly symptomatic NT-SCD children (65 +/- 7%). Non-invasive measurements of brain tissue oxygenation with NIRS revealed that abnormal oxygen saturation levels in SCD patients correlated with the severity of their clinical manifestations. Additionally, cerebral oxygen balance seems to be favorably affected by erythro-cytapheresis.