PURPOSE: Kawasaki disease (KD) is an acute febrile vasculitis and the leading cause of acquired heart disease in children. However, early diagnosis of KD remains challenging, and its pathogenic mechanisms are yet to be fully elucidated. This study utilized Olink Targeted Proteomics to analyze serum protein profiles and identify potential early diagnostic biomarkers for patients with KD. METHODS: Based on febrile children final diagnosis, they were categorized into either the KD group or the febrile control (FC) group. Serum samples from each group were randomly selected and analyzed using the Olink Target 96 Inflammation panel. A retrospective analysis of clinical data was also conducted. By integrating the results of the Olink analysis with clinical data, receiver operating characteristic (ROC) curve analysis was performed to determine the diagnostic potential and critical thresholds of the identified biomarkers. RESULTS: This study identified 25 differentially expressed proteins, with 18 upregulated and 7 downregulated proteins in the KD group. Using LASSO regression analysis, we identified 5 protein biomarkers, IL-17A, CCL23, SCF, TWEAK, and NT-3, that could be used to distinguish KD from FC. Among these, IL-17A exhibited the greatest fold change. Additionally, a subset of the participants underwent serum cytokine testing within the first 5 days of fever onset during hospitalization. Our retrospective analysis of this clinical data found that IL-17 levels were significantly elevated in children subsequently diagnosed with KD. CONCLUSION: Our results suggest that inflammation-associated serum proteins are strongly linked to KD. Among the identified biomarkers, IL-17 family, especially IL-17A, showed the best correlation, providing clinicians with a new potential biomarker for early diagnosis of KD.