Microplastics are pervasive pollutants in aquatic ecosystems, yet their effects on fish tissues remain insufficiently characterized. Our study investigates the impact of polystyrene microplastics (0.5 and 2 μm) on the gill and intestinal tissues of goldfish (<i>Carassius auratus</i>), with a focus on inflammatory responses and pathogen susceptibility. Following two weeks of exposure, histological and molecular analyses revealed increased filament cartilage thickness in gills, enhanced villus thickness and goblet cell numbers in intestines, and upregulation of immune- and oxidative stress-related genes. Exposure to 0.5 μm microplastics significantly reduced survival after <i>Edwardsiella piscicida</i> infection, indicating increased vulnerability to pathogens. These findings highlight the immunotoxic effects of microplastics and their potential to compromise fish health in contaminated environments.