A soluble form of CD21 (sCD21) and CD23 (sCD23) is released from the surface of human white blood cells upon shedding of the extracellular domain. sCD21 circulates in a complex with cleavage fragments of C3 and sCD23, which were previously identified as ligands of membrane and soluble CD21. sCD21 seems to be a marker of chronic inflammatory disease. To assess the sCD21 and sCD23 status in patients with subsets of juvenile arthritis (JA), we determined plasma levels sCD21 and sCD23. Plasma sCD21 levels were significantly decreased in all JA subtypes (O-JA P < 0.0068; P- and S-JA P < 0.0001) compared to healthy controls. Plasma sCD23 levels were significantly decreased in P-JA and S-JA (both P < 0.0001), but not in O-JA (P < 0.3843) in comparison with healthy controls, and data statistically analyzed. Our results suggest that pathological mechanisms relevant to autoimmune disorders interfere with the regulation of both CD21 and CD23 shedding.