The current investigation sought to determine the impact of Saussurea costus (S. costus) root extract (SCRE) supplementation on cyclophosphamide (CTX)-induced anemia. Forty male albino rats were separated into four groups (10 rats each): Group I (control), Group II (SCRE), Group III (CTX), and Group IV (CTX+SCRE). Blood and femoral bones were collected after the end of the experiment. The following parameters were measured; hematological parameters, erythrocyte oxidative biomarkers, erythrocyte osmotic fragility, and plasma and erythrocyte Na+ , K + and Mg²+ ions levels. Moreover, the histopathological investigation was conducted. The results revealed that the CTX significantly reduced all hematological parameters and bone marrow cellularity. CTX also altered erythrocyte oxidative biomarkers, shifting the osmotic fragility curve to the right and disrupting plasma and erythrocyte Na+ , K + and Mg²+ ions levels. With the supplementation of SCRE, all these parameters improved. So, it could be concluded that CTX-induced anemia resulting from myelosuppression and erythrocyte damage caused by oxidative stress could be mitigated by Saussurea costus root extract (SCRE).