Viral infection of the central nervous system (CNS) results in a rapid influx of bone marrow (BM)-derived monocytes/macrophages, that ultimately induce fatal pathology in the mouse. Whilst these cells are derived from the bone marrow, little is known about the kinetic and migratory events that mobilise BM monocytes and their progenitors in response to CNS infection. The BM is home to a complex system of haematopoietic cells. In contrast to the peripheral immune system where distinct cell populations can be delineated using defined cell surface markers, populations in the bone marrow exist as a haematopoietic continuum of overlapping developmental states rather than fixed populations. These states represent the differentiation of long-term haematopoietic stem cells through various lineage-committed progenitors into mature forms; and this differentiation occurs in concordance with a genetically encoded rise and fall of various overlapping cell surface markers. The complexity of this progression requires high-dimensional single cell technologies to fully unravel, which has so far been unavailable to the disciple of stem and progenitor cell research. However, the rise of both fluorescence and mass cytometry (CyTOF) technologies and novel data analysis software has enabled the study of single cells with up to ~ 40 parameters with minimal overlap of reporter signals. Here we report the analysis of complex BM systems and kinetic changes that occurred in monopoiesis, a system that is not well characterized, during neurotropic viral encephalitis. To do this, we compared fluorescent flow cytometry assays developed on our laboratory to characterize bone-marrow stem and progenitor kinetics, with novel mass cytometry assays run on Australia’s first CyTOF II, acquired by the Ramaciotti Facility for Human Systems Biology.