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Background The serum tumor markers CA 19–9 and CA 125 are the serologic markers used for the monitoring of biliopancreatic and ovarian cancer, respectively. They are reported to be elevated in a variety of nonneoplastic clinical situations, including end-stage liver disease (ESLD). However, their prevalence and degree of elevation in patients with ESLD remained unclear. Aim To examine the prevalence and degree of elevation of CA 19–9 and CA 125 in patients with ESLD and to determine their association with severity of liver disease. Methods Retrospective analysis of 161 patients with ESLD that were evaluated for liver transplantation at our institution between March 2009 and December 2010. The mean age was 55.15 ± 8.75 years and 107 (66.4%) of the patients were men. Serum CA 19–9 and CA 125 levels were determined during evaluation of their candidacy for liver transplantation. Results Eighty-three (51.5%) patients had elevated CA 125 and 44 (53%) of them had a serum concentration >5 times the upper limit of normal (ULN). Elevated CA 125 was associated with alcoholic liver disease, high Model for End-Stage Liver Disease (MELD) score, and presence of ascites. Similarly, 37 (23%) patients had elevated CA 19–9 and 8 (21.6%) of them had a serum concentration >5 times ULN. Elevation of CA 19–9 was associated with high MELD score. Conclusions CA 125 and CA 19–9 concentrations were elevated in 51.5% and 23% of patients with ESLD, respectively. Although the definite etiology remained unclear, their elevation was associated with the pathological conditions associated with advanced liver disease. Further studies are needed to clarify the underlying mechanism(s) responsible for their increased levels.