Objectives Over the last 20 years, tertiary institutions have been subjected to several changes. This has resulted in increased workloads for academics. Some academics have started to experience symptoms that are related to chronic fatigue syndrome and burnout. Researchers, however, cannot agree whether the 2 syndromes are two sides of the same coin or actually 2 separate constructs. This study that was conducted at a tertiary institution in South Africa therefore aimed to determine if these constructs accounted for the evidence of the same syndrome within an academic setting or if they were 2 separate, distinguishable constructs. However, since job satisfaction and social support play a role in the poor physical and psychological health experienced by individuals with chronic fatigue syndrome or burnout, it was decided to also include these 2 constructs into the investigation. Age was also incorporated because it had dissimilar relationships with burnout and chronic fatigue syndrome. Material and Methods The participants completed the following questionnaires via an online survey: the Centers for Disease Control and Prevention Chronic Fatigue Syndrome Symptom Inventory , the Oldenburg Burnout Inventory , the Overall Job Satisfaction Scale and the Social Support Scale . The data was used for constructing a structural equation model. Results Job satisfaction was found to be a strong predictor of burnout. The number of symptoms indicative of chronic fatigue syndrome reported by the participants proved to be a relatively strong significant predictor of burnout. Age did not yield any significant relationship with any of the constructs. Conclusions The results indicated that chronic fatigue and burnout should be perceived as 2 distinguishable constructs in the academic context. It should be noted, however, that some overlap exists between them. Int J Occup Med Environ Health. 2019;32(1):75–85