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Low hemoglobin oxygen saturation (SpO 2 ) is common in Sickle Cell Anemia (SCA) and associated with complications including stroke, although determinants remain unknown. We investigated potential hematological, genetic, and nutritional predictors of daytime SpO 2  in Tanzanian children with SCA and compared them with non-SCA controls. Steady-state resting pulse oximetry, full blood count, transferrin saturation, and clinical chemistry were measured. Median daytime SpO 2  was 97% (IQ range 94–99%) in SCA ( N  = 458), lower ( P  < 0.0001) than non-SCA (median 99%, IQ range 98–100%;  N  = 394). Within SCA, associations with SpO 2  were observed for hematological variables, transferrin saturation, body-mass-index  z -score, hemoglobin F (HbF%), genotypes, and hemolytic markers; mean cell hemoglobin (MCH) explained most variability ( P  < 0.001, Adj  r   2  = 0.09). In non-SCA only age correlated with SpO 2 .  α -thalassemia 3.7 deletion highly correlated with decreased MCH (Pearson correlation coefficient −0.60,  P  < 0.0001). In multivariable models, lower SpO 2  correlated with higher MCH ( β -coefficient −0.32,  P  < 0.001) or with decreased copies of  α -thalassemia 3.7 deletion ( β -coefficient 1.1,  P  < 0.001), and independently in both models with lower HbF% ( β -coefficient 0.15,  P  < 0.001) and Glucose-6-Phosphate Dehydrogenase genotype ( β -coefficient −1.12,  P  = 0.012). This study provides evidence to support the hypothesis that effects on red cell rheology are important in determining SpO 2  in children with SCA. Potential mechanisms and implications are discussed.

Hematological and Genetic Predictors of Daytime Hemoglobin Saturation in Tanzanian Children with and without Sickle Cell Anemia