Abstract Aim of the work To investigate the role of endothelial protein C receptor (EPCR) (membrane and soluble forms) as a biomarker of lupus nephritis (LN) in systemic lupus erythematosus (SLE) patients and to study its relation to the prognosis and response to treatment. Patients and methods The study included 30 SLE patients and 30 matched healthy volunteers as well as 10 renal biopsies from surgical nephrectomy as a control for membranous (mEPCR) examination. SLE disease activity index-2000 and damage index were assessed. Serum sEPCR was measured. Renal expression of mEPCR was analyzed. All patients were reassessed after 3 months. Results Patients were 26 females and 4 males with a mean age of 29.6 ± 10.04 years and disease duration of 4.4 ± 3.5 years. Their mean SLEDAI was 13.9 ± 9.9 and damage index 1 ± 1.5. Serum levels of sEPCR were significantly higher in patients with LN (19.9 ± 5.7 ng/ml) than those without (8.95 ± 4.2 ng/ml) and controls (5.3 ± 2.6 ng/ml)(p Conclusion sEPCR plays a role in the pathogenesis, is related to a bad prognosis and poor response to treatment in LN. mEPCR was not related to LN grading.