Vibrio parahaemolyticus and microplastics are prevalent in the ocean. Bacteria attach onto plastic particles, forming harmful biofilms that collectively threaten bivalve health. This study investigates the interaction between polyamide microplastics (PA: particle size 38 ± 12 μm) and V. parahaemolyticus, as well as their combined impact on thick-shelled mussels (Mytilus coruscus). We introduced 10¹¹ CFU/L of V. parahaemolyticus into varying PA concentrations (0, 5, 50, and 500 particles/L) to observe growth over 14 hours and biofilm formation after 48 hours. Our findings indicate that microplastics suppress biofilm formation and virulence gene expression. Four treatments were established to monitor mussel responses: a control group without PA or V. parahaemolyticus; a group with 50 particles/L PA; a group with 10¹¹ CFU/L V. parahaemolyticus; and a co-exposure group with both 50 particles/L PA and 10¹¹ CFU/L V. parahaemolyticus, over a 14-day experiment. However, combined stress from microplastics and Vibrio led to immune dysregulation in mussels, resulting in intestinal damage and microbiome disruption. Notably, V. parahaemolyticus had a more severe impact on mussels than microplastics alone, yet their coexistence reduced some harmful effects. This study is the first to explore the interaction between microplastics and V. parahaemolyticus, providing important insights for ecological risk assessments. Environmental ImplicationVibrio parahaemolyticus is a prevalent marine pathogen that significantly affects the health of bivalve shellfish. Concurrently, global plastic pollution raises concerns, as microplastics can transport and enhance pathogen exposure. This study examines the impacts of polyamide microplastics and Vibrio parahaemolyticus on thick-shelled mussels (Mytilus coruscus). We assessed immune responses, intestinal damage, and gut microbiota disruptions using 16S rRNA sequencing, qRT-PCR and histopathology. Our aim is to improve the understanding of polyamide microplastics and pathogenic bacterium pollution in aquatic systems.