BACKGROUND & OBJECTIVES As a result of immune defects in Sickle cell disease (SCD), affected individuals are prone to infection from encapsulated bacterial pathogens like Streptococcus Pneumoniae. Studies on the etiological agents of bacteremia in children with SCD in Nigeria are few and have revealed a spectrum of organisms that is different from those recorded in other parts of the world. AIM AND OBJECTIVES The objectives of this study were to determine the prevalence of bacteremia, etiological agents and antibiotic susceptibility pattern in febrile children with SCD attending the University College Hospital (UCH), Ibadan, Nigeria. METHODS The study was cross-sectional and took place at the Department of Pediatrics of the UCH, Ibadan. Children with SCD, ages 0-17 years presenting with axillary temperature ≥ 38°C were enrolled after obtaining informed consent. History was obtained and complete physical examination performed after which blood was collected for culture and antibacterial susceptibility tests. RESULTS A total of 116 children were studied of which 69 (59.5%) were males, 111 (95.7%) were of the Hemoglobin SS phenotype and 5 (4.3%) of the Hemoglobin SC phenotype. Bacteremia was present in 16 (13.8%) of the 116 children. Gram negative bacteria constituted 10 (62.5%) of all isolates, while the predominant isolates were Klebsiella pneumoniae 4, (25%) and Staphylococcus aureus, 4 (25%). Over 80% of the isolates were susceptible to Ceftriaxone, Amikacin and Meropenem. CONCLUSIONS Klebsiella pneumoniae and Staphylococcus aureus are the predominant causes of bacteremia in children with SCD in Ibadan, contrary to findings in western countries.