Microplastics (MPs) and nanoplastics (NPs) (MNPs) are hazardous to ecosystems, wildlife, and through seafood, also for human health. Due to biological, chemical, and physical characteristics, NPs can slip through cell membranes, being even more toxicologically important than MPs. Thermal Desorption - Proton Transfer Reaction - Mass Spectrometry (TD-PTR-MS) was used to analyse mussels from the Apulian region, Italy. All the analysed organisms have NPs (values ranging from 10 ng MNPs/ DW mg to 187 ng MNPs / DW mg). The highest mass of plastics was detected in the size groups > 2,2 µm (218 ng MNPs / DW mg) and 20–200 nm (187 ng MNPs / DW mg). An upscaling we performed estimated that people in Europe could ingest more than 2 mg of NPs per year through seafood consumption. The detected presence of nanoplastics in farmed mussels here presented contributes to establishing a baseline for monitoring these pollutants.