Saposin B domain-containing or saposin-like proteins (SAPs, SAPLIPs) have been described as lipid/membrane-binding and often show antibacterial and cytolytic activity. Members of this protein family are present in phylogenetically distant organisms, pointing to their functional importance. Several SAPs are found in trematodes and some of them apparently are related to host-parasite interaction as they show cytolytic activity or immunogenicity. In the present study, we search for SAP genes of Opisthorchis felineus, Clonorchis sinensis and O. viverrini, compare and analyze their structure and expression patterns. We define three orthologous groups of SAPs in opisthorchids and suggest a unique protein motif with unknown function in one group of orthologs.