Hepatocellular damage takes place as a result of ischemia and reperfusion during liver transplantation (LT). To discriminate the type of cell death and quantitate its severity may provide new insights into the mechanisms of hepatocellular damage. Therefore, we investigated the type of cell death by ELISA-based assays in patient sera. Apoptosis was specifically assessed by measuring a novel soluble biomarker, the caspase-cleaved cytokeratin 18, while total cell death (apoptosis and necrosis) by cytokeratin 18 released from dead (necrotic and apoptotic) cells. Twenty-seven live (LDLT) and 14 deceased (DDLT) donor liver transplantations were analyzed before the operation, at the anhepatic stage, first, sixth and 24th hour after the reperfusion. Both apoptosis and total cell death have successfully been demonstrated although they have not been confirmed by the liver biopsy that is impossible to perform in this setting. Apoptosis was not induced in LDLT. Total cell death (primarily necrosis) only transiently appeared the first hour after the reperfusion in LDLT, while it sharply increased the first hour after the reperfusion and maintained its level in DDLT. Soluble cytokeratin 18 biomarkers seem to be useful to discriminate and quantitate the type of cell death during early ischemia and reperfusion periods of LT.