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Introduction: In India, Sickle Cell Disease (SCD) is associated with significant morbidity and represents a major health problem in central India. Patients with SCD are susceptible to a variety of bacterial infections, which are a major cause of morbidity and mortality. The burden of disease caused by bacterial infections in patients with SCD is less studied and have long been neglected. Therefore, there is scarcity of data for the association between SCD and invasive bacterial diseases. So it becomes necessary to have knowledge of distribution of these pathogens and their susceptibility to antibiotics. Aim: To identify the most common bacterial infections among children with SCD and to check antibiotic susceptibility patterns of all the clinical isolates. Materials and Methods: The present study was a descriptive observational study which was conducted in the Department of Microbiology, Government Medical College and Hospital, Nagpur, Maharashtra, India, for two years from October 2013 to October 2015. Paediatric patients of age ≤12 years diagnosed with SCD and admitted in the paediatric wards of this tertiary care hospital, having body temperature ≥38.5°C were enrolled in the study. Clinical specimens i.e. blood, urine, pus, and body fluids such as Cerebrospinal Fluid (CSF), and pleural fluids were collected aseptically and the bacteria causing the infections were isolated and identified conventionally in accordance with the Standard Operating Procedures (SOPs). Antimicrobial susceptibility testing was performed as per the Clinical and Laboratory Standards Institute (CLSI) guidelines 2013 by modified Kirby-Bauer method. Data was presented as numbers and percentages. Results: A total of 824 samples, including blood, urine, CSF, pus, and pleural fluid were collected from 412 SCD patients. Prevalence of bacterial infections among patients with SCD was 17.35%. Bacteraemia was the most common infection among febrile children with SCD 84 (20.38%), followed by Urinary Tract Infection (UTI) 55 (15.02%), osteomyelitis 2 (13.34%), and meningitis 1 (5.56%). Total 143 organisms were isolated from different samples and Gram negative bacilli 106 (74.12%) were found to be the commonest cause of bacterial infections among children with SCD. Imipenem was the best antibiotic for infections with Multidrug Resistant (MDR) Gram negative bacilli. Conclusion: To identify children with SCD and prevent bacterial infections in them should be a priority target for health research as these infections make a large contribution to the morbidity and mortality among children with SCD.