Our study highlights CD8+ natural killer T cells as a percentage of T cells and lymphocytes, CD19 on IgD+ CD38- B cells, absolute monocyte count, CD80 on CD62L+ myeloid dendritic cells, activated and secreting CD4 regulatory T cells as a percentage of CD4 regulatory T cells, CD80 on myeloid dendritic cells, CXCL5, and CCL20 as key contributors to ME/CFS risk. Here, CD8A is linked to myalgic encephalomeyelitis/chronic fatigue syndrome.