Objective: To evaluate whether the levels of soluble form of the Fas apoptosis antigen (sCD95/sFas) varied from those of healthy control subjects in a group of patients with systemic lupus erythematosus (SLE). This was done to determine whether sFas has a role in either the disease activity or the organ damage in SLE. Methods: Serum levels of sFas were measured over a period of 4 y (277 determinations) in 39 Arab patients with SLE and 22 age-, gender-, and race-matched healthy controls using double antibody ELISA. SLEDAI scores for disease activity and SLICC/ACR scores for cumulative organ damage were determined. Serum levels of acute phase reactants, complement, inflammatory cell counts, levels of autoantibodies, and kidney and liver function test results were obtained retrospectively from clinical records. Results: sFas levels were significantly higher in patients with SLE (n = 39, 277 determinations) (0.60 ng/ml ± 0.38) than in healthy controls (n = 22) (0.26 ng/ml ± 0.11) (P < 0.00001). The levels of sFas correlated with SLICC/ACR (r = 0.36; P < 0.02), but not with SLEDAI. sFas correlated with renal and liver function tests measured by s-creatinine (r = 0.38; P < 0.0001), creatinine clearance (r = -0.30, P < 0.001), s-albumin (r = -0.28, P < 0.0001), and ALT (r = 0.35; P < 0.00001), but did not correlate with the levels of acute phase reactants. Conclusion: sFas is elevated in sera of SLE patient. Since sFas correlates with indices of organ damage but not with disease activity, it may be a marker of organ damage in SLE and may act to protect certain organs from further damage by inhibiting Fas-mediated apoptosis.