All patients with positive blood cultures who were admitted to our children's hospital for sickle cell disease and fever over a 27-month period underwent chart review. Of 517 admissions, there were 10 (1.9%) positive blood cultures. These occurred more frequently in children less than two years old and in children with indwelling central venous catheters. All but one would have been considered at high risk for bacteremia at admission owing to an ill appearance, a focus of infection, or a central venous catheter in place. The one patient with a positive blood culture who did not have one of these three criteria had a benign hospital course on parenteral antibiotics with blood cultures turning negative within one day of presentation. Outpatient management strategies with antibiotics in selected children with sickle cell disease and fever merit further study.