Chronic social stress affects mental and bodily functions and is a risk for depression and other stress-related disorders. Depression has been associated with increased leukocytes and reduced erythrocytes in the blood. Chronic stress in rodents recapitulates these blood profiles, and stress-induced leukocyte mobilization promotes depressive-like behaviors. However, the roles and mechanisms of chronic stress-induced anemia remain elusive. Here we found that chronic social stress reduced circulating iron levels and interfered with the iron-dependent erythrocyte maturation in the bone marrow, leading to iron-deficient anemia. However, systemic iron supplementation did not ameliorate this anemia but exacerbated concomitant depressive-like behaviors. These results demonstrate that chronic social stress alters iron metabolism, leading to anemia, yet promoting stress resilience.