Plastic represents 60-80% of litter in the ocean. Degradation of plastic to small fragments leads to the formation of microplastics (MPs <5 mm) and nanoplastics (NPs <1 µm). One of the most widely used and representative plastics found in the ocean is polystyrene (PS). Among marine organisms, the immune system of bivalves is recognized as suitable to assess nanomaterial toxicity. Hemocyte subpopulations [R1 (large granular cells), R2 (small semi-granular cells) and R3 (small agranular or hyaline cells)] of Mytilus galloprovincialis are specialized in particular tasks and functions. The authors propose to examine the effects of different sizes (50 nm, 100 nm and 1 μm) PS NPs on the different immune cells of mussels when they were exposed to (1 and 10 mg·L-1) of PS NPs. The most noteworthy results found in this work are: (i) 1 µm PS NPs provoked higher immunological responses with respect to 50 and 100 nm PS NPs, possibly related to the higher stability in size and shape in hemolymph serum, (ii) the R1 subpopulation was the most affected with respect to R2 and R3 concerning immunological responses and (iii) an increase in the release of toxic radicals, apoptotic signals, tracking of lysosomes and a decrease in phagocytic activity was found in R1.