Objective: The main aim was to report the prevalence and severity of serious bacterial infections (SBI) in children with sickle cell disease at King Abdulaziz Hospital, Al Ahsa, Saudi Arabia to aid in determining whether outpatient management of such cases is appropriate. Methods: We conducted a retrospective chart review of febrile children less than 14 years of age admitted with sickle cell disease 2005 through 2015. Results: During 320 admissions, 25 children had SBIs (8%) including pneumonia (n=11), osteomyelitis (n=8), bacteremia (n=3, all with Salmonella species) and UTI (n=3). All recovered uneventfully. Conclusion: It appears that in the current era, less than 10% of febrile children with sickle cell disease in our center are diagnosed with a SBI. Over an 11-year period, there were no sequelae or deaths from SBI. Given these excellent outcomes, outpatient ceftriaxone should be considered for febrile well appearing children with sickle cell disease if they have no apparent source and parents are judged to be reliable.