Wilson's disease (WD) is characterized by excessive accumulation of intracellular copper in liver and extrahepatic tissues, leading to significant oxidative stress and tissue damage. To date, several diagnostic biomarkers for WD such as serum ceruloplasmin, serum or urine copper levels and copper content in liver have been identified. However, these biomarkers may not be convincing for the diagnosis in some WD patients. To identify additional novel diagnostic biomarkers, we compared the serum protein profiles of asymptomatic childhood WD patients (n=20), without neurologic manifestation or liver cirrhosis, with normal controls (n=13). Fourteen spots, five up-regulated and nine down-regulated (>2-fold), were differentially expressed in WD patients in comparison to normal control on 2-DE. Among them, three spots were down-regulated in both male and female WD. MS/MS analysis revealed that the three spots were complement component C3, complement factor B and alpha-2 macroglobulin. By comparative proteome analysis, complement component C3, complement factor B and alpha-2 macroglobulin, which are related to oxidative stress and inflammation, turned out to be good candidates for novel diagnostic biomarkers for early stages of WD.