Background: To study the protein profile of the serum exosomes of patients with coronary artery aneurysms (CAA) caused by Kawasaki disease (KD). Methods: Two-dimensional electrophoresis (2-DE) was used to identify proteins from the exosomes of serum obtained from children with CAA caused by KD, as well as healthy controls. Differentially expressed proteins were identified using matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry (MALDI-TOF/TOF MS) analysis. Results: Thirty two differentially expressed proteins were identified (18 up-regulated and 14 downregulated) from serum exosomes of children with CAA and were compared to healthy controls. The expression levels of 4 proteins (TN RBP4, LRG1, and APOA4) were validated using Western blotting. Classification analysis and protein-protein network analysis showed that they are associated with multiple functional groups, including host immune response, inflammation, apoptotic process, developmental process, and biological adhesion process. Conclusions: These findings establish a comprehensive proteomic profile of serum exosomes from children with CAA caused by KD, and provide additional insights into the mechanisms of CAA caused by KD.