Microplastics are emerging contaminants in marine environments and represent a main concern to the scientific community. Estuarine ecosystems are hotspots of microplastic pollution, with possible impacts to its communities. Microplastic ingestion has been reported for several marine species, however the toxicity to aquatic biota and the effects on the ecosystems are still poorly studied. Scrobicularia plana has a large pollutants filtration ability and plays a key role in structure and functioning of estuarine communities, therefore it was selected for this work. In this study two size classes of S. plana organisms were exposed to environmentally relevant polystyrene microparticles (1 μm) concentrations (0.00 μg/L to 25 μg/L) by 96h. At the end, the mortality and condition index were determined and performed biochemical analysis to assess the effects on antioxidant defence system. Based on the results, no direct lethal effects or index condition changes were observed, as consequence of the polystyrene exposure. Still it was observed alterations on the antioxidant defence mechanisms and consequently an increase of oxidative damage. Big size class showed dose-dependent responses, with activities induction of total glutathione peroxidase and glutathione reductase, superoxide dismutase activity was inhibited with the exposure, with this inhibition decreasing with the concentration increase, resulted in significantly increase of lipid peroxidation (quantified as TBARS levels), whereas catalase and glutathione-S-transferase activities were not altered. Organisms of the small size class did not show clear alterations of antioxidant biomarkers, with the exception to superoxide dismutase activity that showed the same trend of big size class. This study highlights the adverse effects of polystyrene microparticles on the estuarine clams and suggests S. plana adult organisms as good bioindicator for the presence of polystyrene pollution in aquatic environments, being tGPx, GRed, SOD and TBARS appropriate biomarkers to assess polystyrene microplastic toxicity, with emphasis to GRed and SOD.