Objective: To investigate the prevalence and risk factors of infections caused by extended spectrum β-lactamase (ESBL) producing Escherichia coli (E. coli) in systemic lupus erythematosus (SLE) patients and develop a predictive model. Methods: Three hundred and eighty-four consecutive SLE patients with E. coli infection were enrolled in this retrospective case control study from January 2012 to December 2017. Prevalence and antimicrobial susceptibility pattern were analyzed. Multivariate analysis was performed by binary logistic regression model to determine the risk factors and the predictive model was developed based on it. Results: Of the total 384 isolates of E. coli tested, 212 (55.2%) produced ESBL. The majority of these isolates were from urine (44.3%). Carbapenems and amikacin had good activity against ESBL producing E. coli (>80%). Eleven variables were identified as independent risk factors for ESBL producing E. coli infection including daily prednisone dose >30 mg (OR=5.48; 95%CI 3.12–13.72), low C3 levels (OR=2.17; 95%CI 1.62–6.71), nosocomial acquired infection (OR=4.12; 95%CI 1.98–8.85), etc. The model developed to predict ESBL producing E. coli infection was effective, with the area under the receiver operating characteristic curves of 0.831 (95%CI 0.755–0.892). Conclusion: The prevalence of ESBL producing E. coli is increasing with high antibiotics resistance in patients with SLE. The model reveals excellent predictive performance and exhibits a good discrimination.