<p>Infections in the central nervous system result in immune cell trafficking into the brain and microglial activation, which may influence Alzheimer’s Disease neuropathology. <i>Toxoplasma gondii</i> infection induces a robust neuroimmune response and a reduction in amyloid plaques in the brains of Alzheimer’s model mice. We investigated the myeloid cell response in the immediate vicinity of amyloid plaques in the brain by injecting 3-month-old 5xFAD mice with <i>T. gondii</i> or PBS as a control. <i>T. gondii</i> chronic infection (6 weeks) resulted in reduced amyloid plaque area, volume, and intensity in the cortex, and plaques with decreased circularity based on 6E10 and Thio-S staining. The brains of <i>T. gondii</i>-infected mice also had increased <i>AIF1</i>,<i> AXL</i>, and <i>CLEC7A</i> transcripts for disease-associated microglia (DAM), and elevated IBA1, MAC2, and CD68 phagolysosomal colocalization with amyloid, indicating myeloid cell activation around plaques. CD4 and CD8 T cells were also increased near amyloid and IBA1⁺ cells in <i>T. gondii-</i>infected mice. To determine the extent of peripheral myeloid cell recruitment to amyloid, bone marrow from CAG-CFP mice was transplanted into irradiated, head-shielded 5xFAD mice prior to infection. Cyan⁺ cells were found surrounding plaques in the brains of <i>T. gondii-</i>infected mice and were comprised predominantly of Ly6C^lo patrolling monocytes, followed by Ly6C^hi inflammatory monocytes and T cells. In addition, the majority of myeloid cells and T cells recruited to the brain were derived from skull bone marrow. These data demonstrate that <i>T. gondii</i> infection increases the infiltration of monocytes and T cells from the skull bone marrow niche and the recruitment of highly activated myeloid cells surrounding amyloid plaques in the brains of 5xFAD mice.</p>