We identified naturally occurring urine peptides with specificity for active systemic SJIA compared with other sources of fever. We hypothesized that SJIA flare is associated with increased levels of circulating mediators of inflammation that activate catabolic pathways leading to the generation of novel peptide biomarkers that are found in urine. We tested this hypothesis through global LC-MS analysis of urine and plasma peptides as well as targeted analysis of plasma proteins using antibody arrays.