Abstract Background Kawasaki Disease is a paediatric inflammatory disease associated with self-limiting vasculitis. It has a world-wide distribution with an ethnic bias towards East Asian populations and is the most common cause of acquired heart disease in children in developed countries. The immunopathogenesis of KD remains poorly understood. The presence of antibody-antigens (pathogen) known as immune complexes in the blood of children with KD was established in numerous studies leading to the hypothesis that immune complexes contribute to the damages of the coronary artery. Methodology Using proteomic technologies we characterised the composition of immune complexes in KD and compare the immune complexes in KD with those in children with other febrile illnesses, TB and healthy children. Immune complexes were precipitated from the blood of 80 children with KD, 80 children with other febrile conditions, 30 with TB and 30 healthy children. We used Lumos Orbitrap mass spectrometry to identify the recovered proteins. Using the bioinformatics program PEAKS, we performed database searches and compared the protein abundances between the different comparator groups. Conclusions Immune complexes isolated from children with KD are different from those recovered from other febrile illnesses in terms of the nature of proteins within the complex. The pattern of proteins in the immune complexes containing immunoglobulins, complement proteins as well as other serum proteins, provides insight into the nature of the unique inflammatory response in KD versus the other inflammatory diseases.