Zinc and Copper released into the environment, through mining and waste combustion in Nigeria, are major threats to fish production. In this study, the sub-acute toxicity of Zinc and Copper to a commercially important fish species was investigated. Three hundred and fifty Heterobranchus bidorsalis (mean weight: 13.5±1.0g, total length: 15.0±0.5cm) were exposed to four different concentrations of copper and zinc for 96 hours in a static renewal bioassay to assess lethal concentration (LC50). The toxicity on fish was assessed using hematological and histopathological indices. The Median Lethal Concentration (LC50) was determined using probit method. The LC50 for copper and zinc were 15.03mg/L and 324mg/L, respectively. Death of fish occurred after 12 hours in the highest concentration of 2000mg/L for zinc treatment and 24 hours in the highest concentration of 80mg/L for copper treatment. The mean percentage mortalities for zinc concentrations of 0.00, 200, 400, 900, 2000 mg/L were 0, 10%, 63%, 100% and 100%, respectively. While mean mortalities for copper concentrations of 0.0,10, 20, 40, 80 mg/L were 0, 10%, 77%, 100% and 100%, respectively. Exposure to copper resulted in frenzied swimming, mucus covering the body and death with their mouths wide open. Similar observations were seen for fish exposed to zinc except that after the death of the fish, there was a release of blood around the gill area. Significant decreases were observed for red blood cells, park cell volume, haemoglobin, and white blood cells, while increases were observed for mean cell volume and mean cell haemoglobin after 96 hours of exposure. Lesions observed include vacuolation, necrosis, cellular infiltration, irregular lamellae, severe sub mucosal congestion, degeneration of cells, haemorrhage and spongiosis in the gills, liver and brain of exposed fish. This study revealed that high doses of zinc and copper are harmful to Heterobranchus bidorsalis juveniles.