['Sphingolipids constitute bioactive molecules with functional implications in homeostasis and pathogenesis of various diseases. However, the role of sphingolipids as possible disease biomarkers in chronic liver disease remains largely unexplored. In the present study we used mass spectrometry and spectrofluorometry methods in order to quantify various sphingolipid metabolites and also assess the activity of an important corresponding regulating enzyme in the serum of 72 healthy volunteers as compared to 69 patients with non-alcoholic fatty liver disease and 69 patients with chronic hepatitis C virus infection. Our results reveal a significant upregulation of acid sphingomyelinase in the serum of patients with chronic liver disease as compared to healthy individuals (p<0.001). Especially in chronic hepatitis C infection acid sphingomyelinase activity correlated significantly with markers of hepatic injury (r=0.312, p=0.009) and showed a high discriminative power. Accumulation of various (dihydro-) ceramide species was identified in the serum of patients with non-alcoholic fatty liver disease (p<0.001) and correlated significantly to cholesterol (r=0.448, p<0.001) but showed a significant accumulation in patients with normal cholesterol values as well (p<0.001). Sphingosine, a further bioactive metabolite, was also upregulated in chronic liver disease (p<0.001). However, no significant correlation to markers of hepatic injury was identified.'] Is serum acid sphingomyelinase upregulated in chronic hepatitis C infection and non alcoholic fatty liver disease?