Serum proteins enriched by 37 different lectins were analyzed by LC-MS/MS. It was found that the enrichment process with Solanum tuberosum lectin (STL) and Lycopersicon esculentum lectin (LEL) detected many trace proteins in the serum. In addition, combinations of lectins were examined, and the combination of STL and LEL was found to be optimal for observing serum trace proteins. The enrichment method by STL/LEL was able to collect trace proteins from sera of various animal species as well as humans. We further applied this STL/LEL method to systemic lupus erythematosus (SLE) models and control mouse serum to search for serum proteins altered by SLE.