Plastic pollution poses a global threat to aquatic organisms, yet its effect on many species remains poorly docu-mented and understood. This study addresses the impact caused by different sizes of polyethylene (PE) plasticson the common carp and evaluates their multi-biomarkers response. We investigated the histological structureand measurement of biochemical alterations, antioxidant enzymes, immunological responses, andfluctuationsin blood profiles of the organisms after 15 days of exposure to a concentration of 100 mg/L of nano- (NPs),micro- (MPs) and macroplastics (MaPs). Thefish health status was altered in the sole presence of PE particles.All biomarkers changed after exposure compared to the control group, with larger changes being observedwith the decreasing size of particles (NPs > MPs> MaPs) compared to theirabsence.A synergistic effect resultingfrom the individual impact of plastics penetration in the circulatory system, bursting biochemical responses, andlesions in tissues, might explain the more considerable impact of NPs compared to MPs and/or MaPs.