The effects of vanadium pentoxide (V2O5) on hematological, oxidative stress biomarkers, and histopathological status of male Oryctolagus cuniculus were investigated on a 21-day exposure trial and 7-days recovery. Oryctolagus cuniculus (433.45 ± 5.00 g) were randomized into four experimental and one control groups each in triplicate of four animals. A 96-h estimated median lethal dose (LD50) of 119.0 mg/kg was used to derive four experimental daily oral doses (1, 5, 10 and 20 mg/kg body weight) of V2O5; while the control received distilled water instead. Hematological and oxidative stress biomarkers were evaluated on day-7 (d-7), d-14, d-21 and 7-d withdrawal, whereas histopathology was assessed on d-21 and 7-d withdrawal. After 21-d exposure to 20 mg/kg of V2O5, the red blood cell count (RBC) and hemoglobin concentration (Hb) decreased by 16.9% and 12.3% respectively, while the white blood cell count (WBC) increased by 6.7% compared to the control. The activities of catalase and superoxide dismutase decreased by as much as 30.0% and 14.3% respectively compared to the control in rabbits exposed to 20 mg/kg of V2O5. Lipid peroxidation increased from exposure to V2O5, and peaked on d-7 (∼ 42.9 – 61.0% above the control). Changes in oxidative stress biomarkers were dose- and time-dependent. Sections of the liver and kidney of exposed animals showed alterations in tissue architecture that were characterized by inflammatory cells infiltration, sinusoidal congestion, renal cast formation and vacuolar and tubular degeneration. Taken together, exposure to V2O5 exerts hematological, oxidative stress and histopathological changes in O. cuniculus and calls for strict restriction on the use of this compound to avert environmental hazard.