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During MPXV infection, macrophages are recruited at the site of infection and are thought to contribute to the spread of the virus. Cases of MPXV vertical transmission were reported in infected pregnant women to the developing fetuses <jats:italic>in utero<\/jats:italic> resulting to high viral burden in placenta tissue and abortion. We aim to understand the impact of MPXV infection at the foeto\u2010maternal interface by focusing on macrophages functions. Using full\u2010term placental explant model, macrophages were recruited at site of infection. Isolated naive macrophages are permissive to MPXV infection and secrete high levels of pro\u2010inflammatory cytokines associated with a strong M1 polarization profile. Analysis of antiviral gene expression reveals upregulation of <jats:italic>IFNA<\/jats:italic> and IFN\u2010associated genes suggesting that MPXV induces the expression of some component of antiviral response from macrophages that are unable to clear the virus. Our study shows that macrophages are permissive to MPXV that subverts inflammatory and antiviral machinery without virus clearance. 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