Background: Many toxicity studies have shown that heamatological and histological alterations are widely used as good bioindicators in determining the effect of toxicants on fish. This study investigated the acute toxicity effects of the leaf extract of Thevetia peruviana on full blood count parameters and some organs of Clarias gariepinus juveniles”. Methods: One hundred and twenty C. gariepinus mixed sex juveniles were exposed to acute con-centrations (0.63, 1.25, 2.50, 5.00, and 10.00g/L ) of leave extract of T. peruviana in twelve 20 L capacity rectangular glass tanks with six treatments and bi-replicated. Blood for full blood count was collected through cardiac puncture while gills and liver were excised and analyzed for histo-pathological alterations. Results: PCV, RBC, Hb, Neu, and Lym of C. gariepinus juveniles inversely decreased while WBC directly increased with acute concentrations of T. peruviana leaves extract. The microscopic examination of the gills revealed concentration-dependent histo-architectural alterations expressed as epical clubbing, haemorrhage, desquamation, atrophy, and complete erosion of secondary lamel-lae. The liver showed moderate to severe concentration-dependent histopathological lesions typi-fied by hypertrophy, atrophy, necrosis, kupffer cell proliferation, and hepatocellular degenerations. Conclusion: Given the alterations in the blood, gills and liver noted in this study, the invasive growth of the T. peruviana plant should be controlled to minimize unwanted fish kill.