Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is a severe physically and mentally disabling illness that demonstrates consistent immunological dysfunction. Natural Killer (NK) cells in particular are compromised in CFS/ME, with reduced NK activity being the most consistent immunological biomarker of the illness. Few studies have examined a wide range of innate immune cells, including NK, dendritic cells, monocytes and neutrophils in CFS/ME patients and these cells have not been examined in patients with varying severities of CFS/ME. The objective of this study was to assess innate immune cells in CFS/ME patients with varying severities based on internationally recognised severity scales. Questionnaires were used to assess CFS/ME patients based on the Centres for Disease Control and Prevention Case Definition and severity was determined using the Karnofsky Performance Scale, Dr Bell’s Disability Scale and the Fatigue Severity Scale. Whole blood samples were taken from CFS/ME patients of varying severities and non-fatigued controls (n=65). Samples were stained with monoclonal antibodies and examined via flow cytometric analysis. The data confirmed differences in the innate immune cells of CFS/ME patients in conjunction with the varying severities as well as in comparison to the non-fatigued control group. The role of a severity scale analysis in CFS/ME patients has been demonstrated by this research. Also, previous research has confirmed that immune cell dysfunction is present in CFS/ME patients and this study shows that innate immune cells may be of particular importance in the potential pathomechanism CFS/ME.