Oxidative stress (OS) appears to play a pivotal role in many medical conditions. This study aimed to investigate whether OS is associated with Kawasaki disease (KD) or not, and if so, then to determine whether the mechanism of intravenous immunoglobulin therapy (IVIG) is associated with scavenging reactive oxygen species. Results show a significant difference between patients with KD and those with febrile illnesses (p = 0.018) in terms of OS, as assessed by the d-ROMs/BAP ratio, an arbitrary index comprising derivatives of reactive oxygen metabolites (d-ROMs) relative to a biologic antioxidant potential (BAP). Furthermore, children with KD had a significantly decreased d-ROMs/BAP ratio after IVIG (p = 0.011). Interestingly, the d-ROMs/BAP ratio decreased in 12 of 14 patients with KD who defervesced after IVIG, whereas all but one patient who did not defervesce showed an increase in this ratio. In conclusion, OS plays an important role in the pathogenesis of acute KD. Because IVIG therapy relieves OS by augmenting BAP, an assessment of OS in the acute phase of KD may be useful for early recognition of the necessity to perform additional IVIG treatment. Further study to elucidate this point would be worthwhile.