Experiments were conducted to investigate the health of fish Channa punctatus inhabiting heavy metal-loaded waste water. Heavy metals in the order of Fe > Mn > Zn > Co > Ni > Cu = Cr were present in the waste water. Gills had high metal load followed by liver and then kidney. Albumin, albumin to globulin (A:G) ratio, triglyceride, high density lipoprotein (HDL) and very low density lipoprotein (VLDL) were found to be lower but phospholipid, low density lipoprotein (LDL), total protein, lipid and cholesterol were higher as compared to the reference. Oxidative stress markers such as superoxide dismutase (SOD), catalase (CAT), glutathione S transferase (GST) and lipid peroxidation (LPO) were significantly higher in all tissues, whereas reduced glutathione (GSH) levels were comparatively low. Damage to DNA was observed with significantly higher mean tail length of comets in the exposed fish gill cells (30.9 µm) followed by liver (24.3 µm) and kidney (20.6 µm) as compared to reference fish (5.2, 4.8 and 5.9 µm respectively). Histopathology in gill, liver and kidney also showed marked damage. Integrated biochemical, oxidative stress, genotoxicity and histopathological findings are valuable biomarkers for native fish adaptive patterns, and monitoring of water quality/pollution of freshwater ecosystems.