The present study investigated the effects of polyvinyl chloride (PVC) microparticles (MP) on hepatic antioxidant enzymes activities, serum biochemical and liver histology of juvenile Clarias gariepinus. A total of 180 (25.15g average weight) C. gariepinus were fed PVC MP (95.41 ± 4.23μm) spiked diets at 0.5, 1.5, 3.0 percentage inclusion levels and a control diet for 45days of exposure, then followed by 30days of depuration trials. Fish specimens (9) from each treatment were sampled every 15-day interval for serum biochemical, liver antioxidant enzymes and histopathological assay. Glucose and triglyceride levels increased significantly in PVC-treated groups when compared with the control. Protein levels of 0.5% and 3.0% PVC-treated groups reduced significantly on the 15th and 30th day exposure periods, while serum enzyme activities of all PVC-treated groups increased significantly in a time-dependent manner. Antioxidant enzymes (superoxide dismutase, glutathione peroxidase, catalase) activity in the liver of the treated groups also decreased progressively in a time-dependent manner. A time-dependent elevation in lipid peroxidation levels was observed in PVC MP-treated groups. Histopathological assessment of the fish liver showed mild to severe levels of glycogen depletion, fatty vacuolation and degeneration, hepatocellular necrosis in PVC-treated groups with reference to the control. The present study revealed that PVC microplastic induced oxidative damage and hepatic histopathological alterations in the exposed fish.