Introduction: Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular injury, autoimmunity and tissue fibrosis. Usually collagen type V (V Col) is found hidden between the heterotypical fibers. It was discovered in the rheumatology department at the University of São Paulo (FMUSP) that deposition of this collagen occurs, however with anomalous morphology in SSc patient's tissue, suggesting that V Col is an important molecule in fibrosis and autoimmunity process. The V Col molecule, which has atypical morphology aspect, exposed after a nonspecific inflammatory damage could result in formation of immune complexes (V Col-anti-V Col), whose deposition on the vascular endothelium, would cause a vascular damage, allowing the influx of cells of innate immunity into the extracellular matrix, resulting in an enzymatic degradation of the heterotypical fibers, with exposure of more V Col and perpetuation of the disease. Objectives: Assess whether there is a correlation between anti-V Col's presence in the serum of patients with SSc and indexes of activity, severity and quality of life measured by sHAQ. Methods: Were evaluated 60 patients with SSc diagnostic during the period of January to December 2014. Were applied Medsger severity criteria, Valentini activity criteria and health assessment questionnaire in SSc (sHAQ) in the patients, at initial assessment (baseline) and after 6 months, correlating the presence of anti-V Col with the clinical and laboratory manifestations found. Results: Most patients were female (98.3%) and had the limited form of the disease (43.3%), average age 51 years, white, average duration of nine years of disease and modified Rodnan Skin Score of 13.08. The main clinical manifestations observed in each organic system of patients were: skin thickening in the hands (78.3%), Raynaud's phenomenon (100%), arthritis (33.3%), oesophageal involvement (71.7%), interstitial lung disease (45%), pulmonary arterial hypertension (PAH) (19.4%) and scleroderma renal crisis (SRC) (1.7%). The most significant laboratory abnormalities were elevation of inflammatory markers in 41.7% of patients (ESR and CRP), CPK elevation (15%), low complement (C3 and C4) (3.3%), antinuclear antibody (95%), anti-centromere (41.7%), anti-DNA topoisomerase I antibody (26.7%), anti-RNA polymerase III (11.7%), anti-U1-RNP (16.7%) and anti-Ro (SSA) in 11.7% of patients. The anti-V Col was detected in 5 cases (8.3%) and showed statistical correlation with disease activity and scleroderma renal crisis, besides tendency to association with PAH; however, did not correlate with the severity index of disease or any other clinical manifestation, or with specific SSc antibodies. Conclusions: We suggest that disease activity in SSc patients could be determined by serological analysis, to detect the presence of V Col antibodies in the serum of patients with SSc, facilitating the approach of this serious disease. We suggest further studies with larger number of patients in order to confirm the usefulness of this new marker of di...