CPV is a highly pathogenic virus that enters host cells via the TFR, but its pathogenic mechanisms are not fully understood. In this study, we demonstrated that CPV infection induces ferroptosis in CRFK cells, characterized by elevated lipid peroxidation, increased intracellular ferrous iron, a reduced GSH/GSSG ratio, and mitochondrial damage. At the molecular level, CPV downregulated the ferroptosis-inhibiting proteins GPX4 and FTH1 while upregulating NCOA4 and Drp1. Notably, treatment with the iron chelator DFO both inhibited viral replication and attenuated CPV-induced ferroptosis. Collectively, our findings identify ferroptosis as a critical pathogenic mechanism of CPV infection and highlight the therapeutic potential of DFO in controlling CPV by restoring iron homeostasis. These insights provide a mechanistic basis for the development of ferroptosis-targeted antiviral strategies against CPV.