AbstractAn immunocompromised status has been associated with more odds of being infected with Mpox virus (MPXV) and progressing to severe disease. This aligns with the importance of immune competence for MPXV control and clearance. We and others have previously reviewed parallels between MPXV and other viruses belonging to the Poxviridae in affecting the immune system. This article reviews studies providing direct evidence of the MPXV‐immune interactions. The wide‐ranging effects of MPXV on the immune system, from stimulation to modulation to memory, are broadly categorised, followed by a detailing of these effects on the immune cells and molecules, including natural killer cells, macrophages, neutrophils, lymphocytes, cytokines, interferons, chemokines, and complement.