Knowledge of the endemic parasite fauna in freshwater fish is of great importance. Parasites may work together to stress the health of their hosts. Therefore, the present study aimed to focus on the impact of nematode parasitism on Clarias batrachus (C. batrachus) fish health. The objectives of the present study are to evaluate injury to tissues and oxidative damage due to parasitic infestation, which are indications of disturbance of fish health. According to the results of histological examination, the gut, liver, and gills from C. batrachus, infested with nematode parasites were among the organs severely damaged. Due to tissue injury and oxidative stress, malondialdehyde (MDA) levels were increased and disturbed the oxidant/antioxidant ratio. Enzymatic antioxidants like superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were significantly increased, but glutathione reductase (GR) and non-enzymatic antioxidant i.e., glutathione content (GSH) was significantly decreased. Thus, due to these histological alterations, antioxidant levels significantly affected the health of C. batrachus. Next, we also observed hematologically that, red blood cell (RBCs) and hemoglobin (Hb) levels and mineral content were decreased but white blood cells (WBCs) levels were increased. In liver, we have observed decreased protein, lipid as well as moisture, and ash content but there was an increase in the dry content and glucose levels. In serum biochemical parameters i.e., protein, albumin, globulin, and Albumin/Globulin (A/G) ratio was significantly decreased except glucose level (mg/dl). The increased glucose level may be due to the increase in the breakdown of liver glycogen or decreased synthesis of glycogen indicating the hyperglycemic condition in the infested fish. In conclusion, nematode species have a significant impact on the health status of the fish in culture practices.