Background/aims: Serum iron parameters are affected by liver disorders. It is believed that the tests are unreliable in chronic liver disease, and systemic iron overload should be evaluated histologically in these patients. However, the effect of severity of chronic liver disease on serum iron parameters has not been evaluated. Similarly, differences between liver disease- and iron overload-related iron parameter changes have not been clarified. We aimed to describe the effect of severity of chronic liver disease on serum iron tests and to elucidate the differences of liver disease- and iron overload-related iron parameter changes. Methods: Commonly used serum iron parameters were studied in patients with cirrhosis, chronic viral hepatitis and in persons with confirmed hemochromatosis. Cirrhosis cases were categorized according to Child-Pugh classification. Results: We found that cirrhotic persons of any Child-Pugh class had deviations from normal results. Patients with chronic hepatitis had normal serum iron parameters. Total iron binding capacity decreased as liver disease progressed from hepatitis toward Class C cirrhosis (r= -0.53, p<0.001). Changes in ferritin and transferrin saturation were essentially opposite to this trend (r=0.3, p=0.01 and r=0.47, p<0.001, respectively). Serum iron level was lower in cirrhosis compared to hepatitis. Increased transferrin saturation and ferritin levels resembling iron overload were limited to Class C cirrhotics. Patients with true iron overload could be easily differentiated from these cases by hyper-ferremia. Conclusion: Aberrant serum iron test results indicate cirrhotic stage in chronic liver disease. Cirrhosis and systemic iron overload cause characteristically different changes in serum iron parameters.