In the past years, the research focus on effects of microplastics (MP) on aquatic organisms shifted from marine systems towards freshwater systems, where microplastics occur in similar concentrations. An important freshwater model organism in the MP field is the cladoceran Daphnia, which inhibits a central role in ecosystems and has been established as a test organism in ecotoxicology. Chronic exposure of Daphnia magna (n = 30) to polystyrene (PS) microparticles led to a significant (p-value ¡ 0.001) reduction in body size and number of offspring. The aim of our study was to shed light on underlying molecular effects induced by microplastic ingestion in D. magna. Since proteins, e.g. enzymes are specifically relevant for the physiology of an organism, we assessed beside morphology and life history parameters, the effects of PS MP at the proteomic level. Animals (n = 30) from the same clone, cultured under the same condition served as controls. By the use of a sophisticated mass spectrometry-based approach, we were able to identify 28696 different peptides which could be assigned to 3784 different proteins. Using a bioinformatic workflow, customized for D. magna data, we found 44 proteins being significantly altered in abundance (FDR ¡ 0.05) in the PS treated samples. Among the proteins increased in the PS treated group were several transferases (e.g. GABA transaminase and different sulfotransferases), which are i.a. involved in catalyzing the degradation of neurotransmitters and survival of cells. In the downregulated group we found proteins connected to biotic- and inorganic stress and reproduction. Strikingly, we were able to identify four digestive enzymes which are significantly downregulated in the PS treated animals, indicating a limited nutrient uptake. This could also explain the significantly smaller body length and increased mortality of the treated daphnids, previously observed.