The impact that microplastics have on baleen whales is a question that remains largely unexplored. This study examined the interaction between free-ranging fin whales (Balaenoptera physalus) and microplastics by comparing populations living in two semi-enclosed basins, the Mediterranean Sea and the Sea of Cortez (Gulf of California, Mexico). The results indicate that a considerable abundance of microplastics and plastic additives exists in the neustonic samples from Pelagos Sanctuary of the Mediterranean Sea, and that pelagic areas containing high densities of microplastics overlap with whale feeding grounds, suggesting that whales are exposed to microplastics during foraging; this was confirmed by the observation of a temporal increase in toxicological stress in whales. Given the abundance of microplastics in the Mediterranean environment, along with the high concentrations of Persistent Bioaccumulative and Toxic (PBT) chemicals, plastic additives and biomarker responses detected in the biopsies of Mediterranean whales as compared to those in whales inhabiting the Sea of Cortez, we believe that exposure to microplastics because of direct ingestion and consumption of contaminated prey poses a major threat to the health of fin whales in the Mediterranean Sea.