Measurements of the saturation of arterial blood with oxygen (SaO2) were compared in 24 children during sickle cell crises. Simultaneous pulse oximetry (Nellcor N-100 pulse oximeter) and arterial blood analysis showed that SaO2 measured by pulse oximetry overestimated cooximeter-measured SaO2 (mean bias, 6.9%; p < 0.001). The blood gas machine-calculated SaO2 also overestimated cooximeter-measured SaO2 (p < 0.001). The bias increased with increasing age (p = 0.002) and carboxyhemoglobin level (p = 0.005) but was not related to methemoglobin, total hemoglobin, percentage of hemoglobin S, or percentage of hemoglobin F.