Cadmium (Cd) is an environmental heavy metal that enters the body through ingestion or inhalation. Following absorption, Cd is transported through the bloodstream and can damage red blood cells (RBCs), causing reduced membrane stability and phosphatidylserine (PS) exposure. These changes may promote the recognition and engulfment of damaged RBCs by macrophages. However, erythrophagocytosis of Cd-damaged RBCs and the associated macrophage inflammatory response remain unclear. We investigated Cd-induced RBC damage, erythrophagocytosis, and inflammation. Mouse RBCs were treated with Cd, and PS exposure was assessed by flow cytometry. Cd treatment concentration-dependently increased PS exposure. Damaged RBCs were co-cultured with bone marrow-derived macrophages, and erythrophagocytosis was monitored by confocal live-cell imaging. Time-dependent interactions and engulfment of Cd-damaged RBCs by macrophages were observed. ELISA showed that macrophages co-cultured with Cd-damaged RBCs secreted higher levels of TNF-α and IL-1β than those co-cultured with control RBCs. These findings indicate that Cd induces PS exposure in RBCs and suggest that erythrophagocytosis of Cd-damaged RBCs is associated with increased inflammatory cytokine secretion by macrophages. [This research was supported by the Manufacturing Human Cell-based Artificial Blood and Platform Technology Development for Transfusion, funded by the Multi-Ministerial Research Project, Republic of Korea (RS-2023-KH140699).]