Multisystem inflammatory syndrome in Children (MIS-C) occurs in children between two and six weeks following an initial SARS-CoV-2 infection. The mechanism through which a minority of children develop the hyperinflammation characteristic of MIS-C, while others remain well, is unknown. In this study we present an in-depth assessment of the proteome of children before and after SARS-CoV-2 infection, including children with MIS-C. Reassuringly, these data show that there were minimal changes to the circulating proteome in healthy children as result of SARS-CoV2 infection and there was no evidence of continued inflammation following SARS-CoV-2 infection in children. However, activation of pro-inflammatory pathways and raised circulating markers of myocardial and vascular damage were found to be significantly associated with MIS-C. Our findings have been verified in silico using publicly available proteomic datasets and hence several promising candidate biomarker proteins for diagnosis of MIS-C are identified and described herein.