Spondin 2 (SPON2) plays an important role in multiple processes and is a member of the Spondin 2/F-spondin family of extracellular matrix proteins. We investigated serum SPON2 levels and its correlation with renal functions and urine protein excretion in different glomerular diseases. The cohort included 97 consecutive adults with persistant proteinuria (>300 mg/day) with the diagnosis of focal segmental glomerulosclerosis (FSGS), membranous glomerulonephritis (MN), IgA nephropathy (IgAN), membranoproliferative glomerulonephritis (MPGN), and AA amyloidosis and the control groups with 15 polycystic kidney disease (PKD) and 32 healthy people. Serum SPON2 levels in MN (64.6 ng/mL), FSGS (47.8 ng/mL), IgAN (52.6 ng/mL), MPGN (54.6 ng/mL), and AA amyloidosis (60.7 ng/mL) groups were higher than those of the control (26.4 ng/mL) and nonglomerular disease groups (PKD) (15.3 ng/mL). Only serum SPON2 levels were correlated with serum uric acid and triglyceride levels in patients with glomerular disease. This is the first study to show that serum SPON2 levels are similar in different glomerular diseases and that there is no correlation between SPON2 and proteinuria grade.