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Objectives SMILES is a multicenter Spanish endeavor focused on a comprehensive molecular characterization of a cohort of lupus patients using transcriptomic, single cell sequencing and microbiome analysis. In this initial report we used baseline clinical data to assess associations between lifestyle features and quality of life (QoL) of these patients.Methods Forty-one Rheumatology departments across Spain participated. We enrolled adults (>=18 years) fulfilling 1997 or 2019 ACR classification criteria for SLE. Evaluation included: medical record review, clinical assessment, blood, urine, fecal and cutaneous microbioma samples and cutaneous biopsies. SLEDAI 2K and BILAG indices for activity evaluation and SLICC disease index (SDI) for damage were used. Lifestyle variables were: smoking, alcohol intake, university education and regular physical exercise. QoL was measured with the LupusQoL across eight domains: physical health, pain, planning, intimate relationships, burden to others, emotional health, body image, and fatigue. Associations were assessed using linear regression models, fit separately for each LupusQoL score (outcome) and lifestyle factor (predictor).Results A total of 220 patients (90% women; mean age 45.8 ± 12.6 years; mean disease duration 12.0 ± 9.8 years) were included. Smoking was significantly associated with poorer results in all LupusQoL domains, whereas university education and regular physical exercise were associated with better results in the large majority of domains ( table 1). Alcohol intake was associated with better QoL; mot drinkers reported only occasional consumption, consistent with a social pattern and correlated with having university studies. No differences were observed for disease activity indices, while smoking was associated with higher damage (SDI, p = 0.05).Abstract PO:13:343 Table 1P values of associations between life-style features and LQoL domains using liner regression modelsConclusions Lifestyle factors show robust associations with QoL in SLE: smoking correlates with poorer QoL, whereas university education and regular physical exercise correlate with better QoL; occasional alcohol intake also correlates with better QoL, likely reflecting social/educational context. Causality cannot be inferred from cross-sectional data; however, from a clinical standpoint these findings support reinforcing smoking cessation and promoting physical activity and health education as part of holistic SLE care.