Tissue turnover, especially in the skin, is altered in systemic sclerosis (SSc), leading to tissue accumulation. The objective was to examine type III, IV, and VI collagens turnovers in SSc and investigate longitudinal alterations in relation to modified Rodnan Skin Score (mRSS). We included patients fulfilling the 2013 ACR/EULAR criteria for SSc (limited cutaneous [lcSSc, n=20], diffuse cutaneous SSc [dcSSc, n=23]) and healthy controls (HC, n=10). Biomarkers of type III, IV, and VI collagens formation (PRO-C3, PRO-C4, PRO-C6) and degradation (C3M, C4M, C6M) were measured in serum. The fibrotic index of the individual collagens (FICol) were calculated. The fibrotic index of type III and VI collagens (FICol3 and FICol6) were increased in dcSSc compared to lcSSc (FICol3: 1.4 vs. 0.8, P=0.0001; FICol6: 1.2 vs. 0.9, P=0.03). The fibrotic index of type IV collagen (FICol4) was not different between the groups but was 1.5 times higher than HC (HC: 6.9, lcSSc 10.4, dcSSc: 10.5). Both FICol3 and FICol6 correlated with mRSS with rho's of 0.59 (P