<h3>Background:</h3> Hospital-acquired bacterial infections significantly contribute to the mortality of patients with systemic lupus erythematosus (SLE). The connection between lupus activity, damage accrual, and the risk of nosocomial bacterial infections is not well-established and may be influenced by various confounding factors. <h3>Objectives:</h3> To assess the impact of disease activity and damage accrual as risk factors for nosocomial bacterial infections in SLE patients. <h3>Methods:</h3> A retrospective multicenter cohort study was conducted, involving 2217 SLE patients from ten institutions in Colombia. The relationship between lupus activity and organ damage with the occurrence of bacterial infection during hospitalization was evaluated. Lupus activity and damage were assessed using Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) scores, respectively. Results were adjusted for confounding variables, including age, sex, chronic renal damage, and the use of glucocorticoids, immunosuppressants, and antimalarials in the preceding month. Logistic regression analyses were performed. <h3>Results:</h3> The median age was 33 years with an interquartile range (IQR) of 24-46. Eighty-seven percent were women, and 60% had lupus nephritis. The median lupus activity was 8 (IQR 2-13), and cumulative damage was 1 (IQR 0-2). The median length of stay and time to the event were 9 (IQR 6-15) and 8 days (IQR 5-14), respectively. There were 321 outcomes (14.5%). See Table 1. Both SLEDAI and SLICC scores were significantly associated with nosocomial bacterial infection, with unadjusted odds ratios (OR) of 1.05 (95% CI, 1.03-1.07) and 1.24 (95% CI, 1.16-1.32), respectively. OR adjusted for the confounding variables considered were 1.08 (95% CI, 1.06-1.10) for SLEDAI and 1.21 (95% CI, 1.12-1.32) for SLICC. See Table 2. <h3>Conclusion:</h3> After adjusting for relevant factors, lupus activity and cumulative organ damage were identified as clear risk factors for hospital-acquired bacterial infections in SLE patients. Each one-point increase in SLEDAI and SLICC scores was associated with an 8% and 21% increased risk, respectively. Additionally, our findings suggest a potential protective effect of antimalarials in this clinical context. <h3>REFERENCES:</h3> [1] Duffy KN, Duffy CM, Gladman DD. Infection and disease activity in systemic lupus erythematosus: a review of hospitalized patients. J Rheumatol 1991;18(8):1180-4. [2] Ramírez-Gómez LA, Velásquez JF, Granda PA, Builes CA, Jaimes F. Asociación de actividad lúpica y el riesgo de infección nosocomial en pacientes de un Hospital universitario en Medellín: estudio prospectivo 2001-2004. Rev Col Reumatol. 2007;14(3):177–86. [3] Zhan Z, Lao M, Su F, Chen D, Liang L, Yang X. Hospital-acquired infection in patients with systemic lupus erythematosus: a case-control study in a southern Chinese population. Clin Rheumatol 2018;37(3):709–17. <h3>Acknowledgements:</h3> We acknowledge the support of the University of Antioquia and the Pan American League of Rheumatology Associations -PANLAR-. Likewise, we thank the following hospital institutions participating in this study: Hospital Alma Máter de Antioquia (Medellín), Hospital San Vicente Fundación (Medellín), Hospital Pablo Tobón Uribe (Medellín), Clínica Universitaria Bolivariana (Medellín), Clínica El Rosario (Medellín), Clínica SOMER (Rionegro), Clínica Universitaria Colombia (Bogotá), Clínica Imbanaco (Cali), Hospital Universitario Del Valle (Cali) and Hospital Serena del Mar (Cartagena). Agradecimientos a la Asociación Colombiana de Reumatología - ASOREUMA, por su apoyo. <h3>Disclosure of Interests:</h3> <b>None declared.</b>