Background: For relapsing polychondritis (RP), no useful biomarkers have yet been identified. We analyzed serum peptide profiles to identify candidate biomarkers. Methods: Patients with RP or rheumatoid arthritis (RA) and healthy control (HC) subjects were divided into training set (RP, n=19; RA, n=21; HC, n=17) and testing set (RP, n=18; RA, n=21; HC, n=18). Seven patients demonstrating granulomatosis with polyangiitis (GPA) were used for validation. The ion intensity of serum peptides was comprehensively measured by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry. Results: One hundred sixty serum peptides were detected. In the RP group of the training set, 24, 8, and 7 peptides showed a ³1.2-fold difference in ion intensity in comparison to the HC, RA, and HC+RA (non-RP) groups, respectively (p the RP/nonRP-4P-2 model provided 83.3% sensitivity and 71.7% specificity in the testing set with GPA group (AUROC, 0.802). Conclusion: Serum peptide profiles provided useful candidate biomarkers for RP and may be implicated in the pathophysiology of RP. Trial registration: University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR), UMIN 000037212. Registered on 30 June 2019.