The aim of this study is to determine the effects of Lead Nitrate and crude oil on the juveniles of the African catfish Clarias gariepinus. The study was based on results of acute toxicity tests, haematological, histopathological, and enzyme analysis. The acute toxicity tests lasting 96 hours were performed on the Clarias gariepinus of mean weight 138 ± 12g and mean total length of 28 ± 1.5cm. The LD50 of Lead Nitrate was 57.5mg/L while LD50 of crude oil was 823.3µl/L (ppm). The experimental fishes used for the chronic toxicity assay were 27.38 ± 0.43cm – 31.18 ± 3.76cm in mean length and 126 ± 3.22g to 151 ± 0.67g in mean weight. They were divided into groups A, B, C, D, and E of 20 fishes each. Group A was kept as control. Group B was exposed to 20mg/L of Lead Nitrate. Group C was exposed to 35mg/L of Lead Nitrate. Group D was exposed to 300ppm while E was exposed to 600ppm of crude oil. Water quality parameters, Dissolved Oxygen (DO), temperature, and pH were monitored. The body weights of the fishes were measured weekly. The experiment lasted for 70 days. Blood samples were collected for haematological and enzyme analysis before dissection of the gills and liver for histopathological examination. The control group showed significant increase in body weight at (P < 0.05) 150g ± 0.85 to 250g ± 7.07 while the treated groups showed significant reduction in body weight, 151g ± 0.67 to 75g ± 10.61. There was no significant difference (P> 0.05) in the water quality parameters DO, temperature, and pH between the control and treated groups. Significant differences (P<0.05) occurred in haemoglobin, haematocrit, red blood cells (RBC) and white blood cells. No significant differences (P> 0.05) occurred in the RBC indices, mean corpuscular haemoglobin concentration(MCHC), mean corpuscular haemoglobin(MCH), mean corpuscular Volume(MCV). Significant differences (P< 0.05) occurred between the serum enzymes: aspartate transaminase(AST), alanine transaminase(ALT), alkaline phosphatase(ALP) of the control and treated groups. The histological sections of the gills and liver showed histopathological lesions in the treated groups. These include hyperaemia, Oedema, necrosis, degeneration and cellular infiltration. The overall effect of Lead Nitrate and Crude oil on the juveniles of Clarias gariepinus was anaemia and weight loss.