Cyclophosphamide (CP) is among the most widely used alkylating anti-cancer agents in chemotherapy. Myelotoxicity is one of its dose-limiting adverse effects. The aim of the present study, therefore, was to investigate the possible protective potential of Vernonia amygdalina (VA) aqueous leaf extract in CPinduced myelotoxicity through evaluation of haematological parameters, glutathione (GSH), lipid peroxidation, antioxidant enzymes (superoxide dismutase (SOD), and catalase(CAT)) as well as histopathological examination of the kidney and liver sections of rats. Outcome was compared with that expressed by MESNA. Administration of CP in a single dose (200 mg/kg, i.p.) significantly (P<0.01) decreased RBCs, WBCs and platelets counts. In addition, CP produced a significant (P<0.01) reduction of all biochemical parameters assayed as well as observable disruption of liver and kidney tissue architectures. Pretreatment of animals with VA (250 mg/kg, per os) daily for 10 consecutive days significantly (P<0.01) ameliorated the changes in haematological and biochemical parameters as well as histopathological changes induced by CP when compared to the CP-treated group. Conclusively, Vernonia amygdalina (VA) aqueous leaf extract could have protective potential against CP-induced myelotoxicity.