Objective: To examine the time trends in hospitalized infections in patients with systemic lupus erythematosus (SLE), and the factors associated with health care utilization and in-hospital mortality. Methods: US National Inpatient Sample data from 1998–2016 were used to examine the epidemiology, time trends, and outcomes of 5 common hospitalized infections in patients with SLE, namely, pneumonia, sepsis/bacteremia, urinary tract infection (UTI), skin and soft tissue infections (SSTIs), and opportunistic infections (OIs). Time trends were compared using the Cochran-Armitage test. Multivariable-adjusted logistic regression models were used to examine the factors associated with health care utilization (hospital stay >3 days, hospital charges above the median, or discharge to a nonhome setting) and in-hospital mortality. Results: Hospitalization rates per 100,000 claims among SLE patients in 1998–2000 versus in 2015–2016 were as follows: for OIs, 1.13 versus 1.61 (1.2-fold increase); for SSTIs, 4.78 versus 12.2 (2.5-fold increase); for UTI, 1.94 versus 6.12 (3.2-fold increase); for pneumonia, 15.09 versus 17.05 (1.1-fold increase); and for sepsis, 6.31 versus 39.64 (6.3-fold increase). In 2011–2012, sepsis surpassed pneumonia as the most common hospitalized infection in patients with SLE. In multivariable-adjusted models, a diagnosis of sepsis, older age, a Deyo-Charlson common comorbidities score of ≥2, having Medicare or Medicaid insurance, and urban hospital location were significantly associated with increased odds of in-hospital mortality and with all health care utilization outcomes. African American race was significantly associated with increased odds of health care utilization. Conclusion: The results of this study indicate that the rates of hospitalized infections increased over time in patients with SLE, and that pneumonia was surpassed by sepsis as the most common hospitalized infection. In addition, associations of risk factors with poorer outcomes were identified. These findings may help inform patients, providers, and policy makers with regard to the burden of infection in SLE, and could lead to interventions/pathways to improve outcomes.