Background: Kawasaki disease (KD) is a form of systemic vasculitis that mainly affects children under the age of five years old. Limb swelling and redness are among the primary symptoms of KD. Previous studies have reported that wireless optical monitoring systems can identify limb indurations characteristics in patients with KD. Therefore, we conducted this study to monitor the dynamic changes in different stages of KD and the disease outcome of coronary artery lesions (CAL).Methods: KD patients who were admitted for intravenous immunoglobulin (IVIG) treatment and controls with or without fever were enrolled in this study. Near infrared spectroscopy data were collected for KD patients at different stages, including before (within one day before IVIG treatment, KD1) and shortly after IVIG treatment (within three days, KD2), at least 21 days after IVIG (KD3), 6 months later (KD4), 1 year later (KD5), 2 years later (KD6), and 3 years later (KD7).Results: This study included a total of 350 pieces of data, including data from 20 healthy controls, 64 fever controls, 53 KD1, 67 KD2, 58 KD3, 28 KD4, 25 KD5, 15 KD6, and 20 KD7. The relative HbO2 of the KD1 group were significantly lower than those of the healthy group (0.298 ± 0.01 vs. 0.304 ± 0.05, p = 0.028) but no significant differences were found with the fever group. The HbT concentrations of KD1 group showed significantly lower than health group (0.632 ± 0.019 vs. 0.646 ± 0.021, p = 0.001) but no significant difference with fever control. Relative levels of HbO2, HbT and Hb showed significant difference between KD1 and health control while StO2 and H2 O showed difference between KD1 and fever control. The relative H2 O concentration was significantly higher in KD patients with CAL formation than without (p < 0.005). Conclusion: This report is the first to use near infrared spectroscopy to detect changes in tissue hemoglobin and water levels at different stages of KD in patients and showed that water content was significantly associated with CAL formation. This non-invasive device may benefit physicians by serving for early identification of KD from fever illness.