Kawasaki disease (KD) is an acute systemic vasculitis that mainly afflicts infants and young children. The symptoms of KD are similar to those of various febrile diseases. Here, we attempted to develop accurate diagnostic biomarkers of KD by performing urine proteomic analysis of samples from healthy controls, patients with KD, and patients with another febrile disease, pneumonia (two patients). We identified differentially expressed proteins (DEPs) in KD as compared to normal controls. We also constructed functional annotation and protein-protein interaction (PPI) networks of DEPs in KD and pneumonia. DEPs common to both KD and pneumonia were identified, as well as DEPs specific to KD. Compared to normal control, 43 and 62 DEPs were identified in KD and pneumonia, respectively. Serine hydroxymethyltransferase 1 is a hub protein of the KD-specific PPI network. Thirteen DEPs common to both KD and pneumonia and 30 DEPs specific to KD were identified. Of these, the expression of eight DEPs could cluster normal and pneumonia samples into one group and cluster KD samples into another group based on hierarchical clustering. Our study identified several DEPs that may play a role in KD and that may serve as diagnostic biomarkers to distinguish patients with KD from both normal control and other febrile diseases.