Schistosoma mansoni is a parasitic helminth that infects millions of people mostly in tropical parts of the world. Different life cycle stages of S.mansoni, that infect or develop in the human host, promote distinct immune responses and are known for their ability to modulate host immune responses. However, the molecular mechanisms through which the parasites interact with, and modulate the host immune system remain incompletely understood. Despite the well-known ability of various lipids to modulate immune responses, a comprehensive analysis of the lipidome of the different life cycle stages has not been performed. Using three complementary MS-based platforms to detect and quantify around 350 lipid species, we here characterized the lipid profiles of S. mansoni cercariae, worms and eggs, as well as extracts and excretory/secretory (ES) products of different life cycle stages of S. mansoni. We identified life cycle stage specific signatures of lipid classes of which cercariae were found to have the most distinct profile. Moreover, we detected several immunolomodulatory oxylipids in the different life cycle stages. Specifically, prostaglandins were found to be most highly enriched in egg preparations, while resolvins were specifically detected in cercariae. Together, the generation of this detailed lipid database of the different life cycle stages of S. mansoni will not only be important for a better understanding of the biology of the parasite itself but also of host-parasite interactions and how that could result in immunomodulation. Display omitted •Comprehensive Lipidomics study of Schistosoma mansoni and its life stages.•Description of a Schistosoma mansoni lipid database.•Identification of several important immunomodulatory lipids, leads for further research.