Carbamylation is a post-translational modification that mostly affects proteins with low turnover, such as dermal proteins. Carbamylated proteins accumulate in skin in an age-dependent manner, contributing to tissue alterations. As dermis is affected by systemic sclerosis (SSc) and anti-carbamylated protein antibodies (anti-CarP Ab) are found in SSc patients, we sought to evaluate the specificity of anti-CarP Ab and their relationship with clinical parameters reflecting skin involvement in SSc. This study investigated serum samples and clinical data from 124 patients with SSc. Anti-CarP Ab were affinity purified from pooled SSc sera, and their specificity was assessed by western blotting and ELISA with carbamylated proteins from two species (human and bovine albumin; human fibrinogen). Anti-CarP Ab were measured in SSc serum samples and in 41 healthy aged-matched individuals. Affinity-purified anti-CarP Ab recognized carbamylated epitopes irrespective of the protein type or species origin. Anti-CarP Ab levels inversely correlated with the modified Rodnan skin score (mRss) (Spearman's R = -0.32, p<0.001), independently of patients' age. Receiver operating characteristics (ROC) analysis identified anti-CarP Ab cut-offs that best discriminated dichotomized clinical variables related to skin involvement: the only clinical variables that were significantly different between groups were mRss (p = 0.001) and scleredema (p<0.001). Low anti-CarP Ab levels were associated with worse skin involvement. Future prospective studies are needed to assess their usefulness in the clinical setting.