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Bacteremia is an important cause of death and complications in children with sickle cell disease (SCD), yet predictors of bacteremia in these patients have not been well identified. The purpose of this study was to test whether clinical and hematologic variables commonly used to predict bacteremia in normal young children with fever could accurately predict bacteremia in febrile children with SCD.The authors reviewed the medical records of all patients with SCD younger than 18 years of age over a 10-year period at a single institution for febrile events. They tested the univariate associations of age, height of fever, white blood cell count (WBC), absolute neutrophil count (ANC), and absolute band count (ABC) with bacteremia. Three separate multivariate analyses were performed using the predictor variables age, temperature, and one of three hematologic variables (ANC, WBC, or ABC) with the outcome bacteremia.There were 175 evaluable febrile events, of which 8 (4.6%) were associated with bacteremia. In the multivariate analyses, all hematologic variables, but not age or height of fever, retained significant associations with bacteremia.In febrile children with SCD, WBC, ANC, and ABC are all independently associated with bacteremia when adjusting for height of fever and age. Hematologic variables may be useful in developing prediction algorithms to identify febrile patients with SCD at higher risk of bacteremia. These data emphasize the need for a national trial to develop a predictive model with defined thresholds.