Background: Systemic lupus erythematosus (SLE) is an autoimmune disease that affects the majority of organs and tissues. SLE flares and bacterial infections are major causes of death in these patients and detection of bacterial infections in them is essential due to different therapy and their clinical manifestations can be similar. Objectives: The objectives of this research were to idenify microorganisms causing bacterial infection in SLE patients and their antimicrobial susceptibility pattern in comparison with bacterial infections in patient with other medical illness in Faculty of Medicine, Mansoura University. Methodology: Urine, blood and other specimens were collected from SLE and non- SLE patients clinically suspected of bacterial infection.. The samples collected were cultivated on blood agar, MacConkey agar, chocolate agar, Sabouraud dextrose agar media (SDA), whereas urine specimens were cultivated on cysteine lactose electrolyte deficient (CLED) and blood samples were inoculated in blood culture bottles. Isolated bacteria were identifed by colonial morphology, Gram stained films and biochemical reactions. Antibacterial susceptibility pattern was determined by disc diffusion method. Results: Urinary tract infection (UTI) was the most common bacterial infection among SLE patients (55%) while bacterial pneumonia was the most common infection in non-SLE patients (50%). Gram negative bacteria were 80.76% of culture isolates in SLE patients while Gram positive bacteria were isolated at a rate of (19.23%). Escherichia coli were the most predominant organism (26.92%). Gram negative bacteria showed highest sensitivity to Piperacillin-tazobactam while Gram positive organisms exhibited 100% sensitivity for Ciprofloxacin, Cefuroxime, Gentamycin and Imipenem. Conclusion: the high morbidity and mortality rates associated with bacterial infections in SLE and its similarity with lupus flare, make accurate detection is very important in order to offer successful treatment and ensure better patient outcome.