Freshwater sediments are a repository of microplastics (MPs) resulting from inland anthropogenic activities. Benthic invertebrates, particularly endobenthic sediment-ingesting species such as the annelid Lumbriculus variegatus (blackworm), are commonly found in contaminated sediments where they likely find and ingest MPs. In the present study, L. variegatus was exposed to concentrations between 0.51 and 20 g kg-1 dry sediment of four size-classes of irregularly-shaped polyethylene MPs (PE-MPs; size-class A: 32-63, B: 63-125, C: 125-250 and D: 250-500 μm) for 48 h to assess their sub-cellular responses to particles ingested, and for 28 days to determine chronic effects on worm's reproduction and biomass. After the short-term exposure (48 h), number of PE-MPs in blackworms' gut were related to MPs concentration in the sediment. In general, PE-MPs ingestion by blackworms induced depletion of their energy reserves (e.g., sugars in all size classes and lipids in the size-classes of PE-MPs > 125 μm), concomitant with the activation of antioxidant and detoxification mechanisms (increased level of total glutathione in all size-classes, and increased glutathione-S-transferase activity in PE-MPs > 250 μm), preventing lipid peroxidation. In addition, it was observed a reduction of aerobic energy production (decreased activity of the electron transport system) and a slight increase in neurotransmission (cholinesterase activity). After a long-term exposure (28 d), the presence and ingestion of PE-MPs did not affect reproduction and biomass of L. variegatus. The activation and efficiency of the antioxidant and detoxification mechanisms allied with the anatomy and physiology of L. variegatus, its feeding strategy and potentially dynamic ingestion/egestion capacity seem to be key features preventing MP deleterious effects under short- and chronic-exposures. Considering the MPs levels reported for freshwater sediments, and despite evidence of MPs ingestion and some sub-organismal effects, our results suggest no adverse impacts of PE-MPs contamination on L. variegatus populations fitness. This study applies an integrative approach in which data concerning the ingestion of different sized MPs and subsequent sub-cellular and apical responses are delivered, raising knowledge on endobenthic invertebrates' strategies to potentially overcome MP toxicity in field contaminated sites.