Erythropoiesis is a highly controlled process partly regulated by the central erythroblastic island macrophage (EI MΦ) which provides iron, growth factors and mediates enucleation of erythroblasts1,2. As macrophages are key effectors of inflammation3, we investigated the effect of bacterial LPS in vivo on erythropoiesis and EI MΦ, defined as CD11b+ F4/80+ VCAM1+ CD169+Ly6G+ in mice4. C57BL/6 mice were injected with 2.5 mg/kg/day LPS for 2 days. LPS administration caused whitening of the bone marrow (BM) with decreased numbers of basophilic (9-fold), polychromatic (3.7-fold), orthochromatic erythroblasts (2.2-fold) and reticulocytes (2.5-fold) and EI MΦ in the BM. This loss of medullar erythropoiesis was compensated by increased number of EI MΦ (13.6-fold), pro-erythroblasts (1.5-fold), polychromatic (1.9-fold), orthochromatic (3.2-fold) and reticulocytes (2.3-fold) in the spleen. As this phenotype resembled suppression of medullar erythropoiesis following G-CSF treatment, we examined whether the mechanism could be indirect via endogenous G-CSF release. LPS induced a transient 80-fold increase in G-CSF concentration in the blood from 123pg/mL to 10ng/ml. LPS was also administered to TLR4 KO and G-CSF receptor (GCSFR) KO mice. These LPS-mediated responses were abrogated in TLR4 KO mice demonstrating that erythropoiesis suppression is TLR4-dependant. However responses in GCSFR KO mice were more contrasted. EI MΦ numbers did not change in GCSFR KO mice and medullar erythropoiesis was still suppressed in KO mice. To further understand how BM erythrocytes could be increased whilst erythropoiesis is suppressed in LPS-treated GCSFR KO mice, we measured vascular leakage by injecting Evans Blue. Blood plasma/femur volume in the BM of LPS-treated GCSFR KO mice was 2.9-fold higher compared to LPS-treated wild-type mice, suggesting that GCSFR-mediated signaling is necessary to maintain the integrity of the BM vasculature in response to LPS. In conclusion LPS-mediated medullar erythropoiesis suppression involves at least two different TLR4-dependent mechanisms in regards to their requirement for GCSFR.