Objective. To investigate the spectrum, antibiotic-resistant pattern, risk factors, and outcomes of infection in patients hospitalized with systemic lupus erythematosus (SLE). Methods. We collected the clinical and microbiological data from hospitalized patients with SLE with infection between June 2005 and June 2015, and then conducted retrospective analyses. Results. Among our sample of 3815 hospitalized patients, 1321 (34.6%) were diagnosed with infection. The majority (78.3%) of infection occurred within 5 years of SLE onset. Bacterial infection was predominant (50.6%), followed by viral infection (36.4%) and fungal infection (12.5%). The lungs (33.7%) and upper respiratory tracts (26.3%) were most commonly affected. Gram-negative bacteria (GNB) were predominant over gram-positive bacteria (178 isolates vs 90 isolates). The most frequently isolated bacteria were Escherichia coli (24.6%), followed by Acinetobacter baumannii (13.4%) and coagulase-negative Staphylococcus (13.4%). Multidrug-resistant (MDR) strains were detected in 26.9% of bacterial isolates. The most common fungus was Candida spp. (99 episodes), followed by Aspergillus (24 episodes) and Cryptococcus neoformans (13 episodes). The overall mortality rate for this cohort was 2.2%; 48 patients died of infection. Factors associated with bacterial and viral infection were higher Systemic Lupus Erythematosus Disease Activity Index, renal involvement, thrombocytopenia, accumulated dose of glucocorticoids (GC), and treatment with cyclophosphamide (CYC). Renal involvement, accumulated dose of GC, and treatment with CYC were associated with fungal infection. Conclusion. Infection was the leading cause of mortality in patients hospitalized with SLE. There were some notable features of infection in Chinese patients including early onset, higher proportion of respiratory tract involvement, predominance of GNB with emergence of MDR isolates, and a variety of pathogens.