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Background: Sickle cell disease (SCD) is a major cause of morbidity and mortality in African children. Infection has been found to be a major cause of hospitalisation, a major precipitant of crises and one of the greatest causes of death among SCD patients at all ages. Objectives: The objective of the study was to determine the prevalence of bacterial infection, pattern of the isolates and the antibiotic sensitivity of isolated bacteria among children with sickle cell anaemia (SCA). Materials and Methods: A cross-sectional study carried out in the University of Maiduguri Teaching Hospital. A total of 242 hospitalised children with SCA with symptoms and signs of infection were recruited for the study using consecutive sampling technique. Sociodemographic and clinical data were obtained. Blood, urine, aspirates, swabs and cerebrospinal fluid samples were collected based on their clinical presentation and subjected to microbiological analysis. Results: A total of 242 patients were studied. The age range was 9 months–15 years, with a mean age of 6.36 years ± 3.75 years. Male-to-female ratio was 1:1.14, with 41.7% of them belonging to low social class. Seventy seven of the 242 had confirmed bacterial infection giving an incidence of bacterial infection in SCA patients of 31.8%. Gram-negative organisms accounted for 64.5% of the isolates and they include Salmonella, Klebsiella, Escherichia coli and Coliforms. However, Staphylococcus aureus (32.9%) was the most frequent microorganism isolated, followed by Salmonella, (20.3%), Klebsiella (12.6%) and Coliforms (12.6%). Amoxicillin-clavulanate, cefixime and gentamicin showed more than 50% activity against the isolated bacterial pathogens while chloramphenicol was found to have low activity against Salmonella. Conclusion: High index of suspicion of bacterial infection should be borne in mind of the attending physician when children with SCA present with features of infection. Detailed clinical evaluation and appropriate sample collection for microbiological analysis are recommended. Empirical treatment should be started on SCA patients who have clinical evidence of infection and should be broad enough to cover for common bacterial pathogens.