Key PointsQuestionWhat are the risks and outcomes associated with the receipt of a diagnostic code for bacteremia in children and young adults with sickle cell disease presenting to the emergency department with fever?FindingsIn this cohort study including 35 548 encounters representing 11 181 individual patients with sickle cell disease, bacteremia was present in 1.1% of the encounters from 36 hospitals. In the multivariable analysis, individuals with a history of bacteremia–associated bloodstream infection and apheresis had higher odds of bacteremia.MeaningThe results of this study suggest that a new episode of bacteremia is an uncommon diagnosis for children and young adults with sickle cell disease presenting to the emergency department with fever; a new diagnosis of bacteremia was significantly more likely if there was a history of a central line placement or bacteremia.