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Background: Systemic lupus erythematosus (SLE) is an autoimmune illness with variable clinical symptoms and disease course. We aimed to identify the Syndecan-1(SDC-1) role in SLE patients with renal involvement, and to determine its correlation with the disease activity & severity. Patients and Methods: This case control research was performed on 30 SLE patients with renal involvement; they fulfilled the 2019 EULAR/ACR SLE Classification Criteria and were collected from outpatient and inpatient clinics of Department of Rheumatology, Rehabilitation, and Physical Medicine at Tanta University Hospitals. Twenty apparently healthy volunteers of matched age and sex were included as controls. Results: Serum level of SDC1 was significantly increased in SLE patients compared to controls. There was a significant negative correlation between SDC1 & C3 level, a significant positive correlation between SDC1 & WBCs, ESR, CRP, blood urea, serum creatinine, 24 h urinary protein, A/C ratio, Anti-dsDNA, SLEDI & illness duration. Conclusions: The SDC1 serum level was significantly higher than controls, and positively correlated with disease activity In SLE patients with LN. [ABSTRACT FROM AUTHOR]