MCTD is a chronic, immune-mediated disorder defined by the combined presence of serum anti-RNP antibodies and distinct clinical features, including progressive lung fibrosis. The aim of the study was to evaluate the potential impact of anti-SSA (i.e. Ro52 and Ro60) and anti-SSB autoantibodies as markers for disease outcomes in MCTD. Stored serum samples from 113 patients included in the cross-sectional, nationwide Norwegian MCTD cohort were screened for the presence of anti-Ro52, anti-Ro60 and anti-SSB by a commercial line immunoassay. Correlation analyses were carried out with clinical parameters, including quantitative lung fibrosis scores by high-resolution CT. Lung fibrosis was defined by reticular pattern changes according to the Fleischner Society CT criteria for interstitial lung disease. Anti-Ro52 antibodies were present in 29%, anti-Ro60 in 19% and anti-SSB in 6% of the MCTD sera. High-resolution CT scoring identified lung fibrosis in 38 of 113 (34%) MCTD patients. Anti-Ro52 antibodies were detected in 50% (19 of 38) of the MCTD patients with lung fibrosis and in 19% (14 of 75) without lung fibrosis (P < 0.001). The odds ratio for the presence of anti-Ro52 antibodies in lung fibrosis was 4.4 (95% CI 1.8, 10.3). Anti-Ro52 antibodies were equally frequent in patients with mild to moderate (eight of 17; 44%) and severe fibrosis (11 of 21; 52%). Anti-Ro52 was not associated with any of the other clinical parameters assessed, nor was anti-Ro60 or anti-SSB. Our cross-sectional data suggest that anti-Ro52 antibodies may serve as a potential marker for lung fibrosis in MCTD.