Free light chains (FLC), considered a biomarker of B cell activity, are frequently elevated in different systemic inflammatory-autoimmune diseases. As systemic sclerosis (SSc) clinical course may be variable, this study aimed to assess FLCs levels in serum and urine of affected individuals, as biomarkers of disease activity. We assessed FLC levels in serum and urine of 72 SSc patients and 30 healthy controls (HC). Results were analyzed in comparison with overall clinical and laboratory findings, disease activity index (DAI) and disease severity scale (DSS). SSc patients displayed increased levels of k and λ FLC in serum, significantly higher than HC (p=0.0001) alongside with the mean levels of free k/λ ratio and of the k+λ sum (p=0.0001). In addition, SSc patients had significant higher levels in the urine of free k and of k/λ ratio than HC (p=0.0001). SSc patients with increased k+λ sum in serum showed a statistically higher levels of erythro-sedimentation rate (p=0.034), C-reactive protein (p=0.003), higher DAI (p=0.024) and DSS (p=0.015) than SSc patients with normal levels of FLC. A positive linear correlation was found between serum levels of free k and DAI (r=0.29, p=0.014). SSc patients with increased free k in urine had statistically higher DAI (p=0.048) than SSc patients with normal level of free k. The significant increased levels of FLC correlated with disease activity in SSc patients. Our results strengthen the role of FLC as useful biomarkers in clinical practice to early diagnosis and monitor disease activity with an improvement of SSc patients’ management.