Background Orthostatic syncope (transient loss of conscious when standing—fainting) is common and negatively impacts quality of life. Many patients with syncope report experiencing fatigue, sometimes with “brain fog”, which may further impact their quality of life, but the incidence and severity of fatigue in patients with syncope remain unclear. In this systematic review, we report evidence on the associations between fatigue and conditions of orthostatic syncope. Methods We performed a comprehensive literature search of four academic databases to identify articles that evaluated the association between orthostatic syncope [postural orthostatic tachycardia syndrome (POTS), vasovagal syncope (VVS), orthostatic hypotension (OH)] and fatigue. Studies were independently screened using a multi-stage approach by two researchers to maintain consistency and limit bias. Results Our initial search identified 2797 articles, of which 13 met our inclusion criteria (POTS n = 10; VVS n = 1; OH n = 1; VVS and POTS n = 1). Fatigue scores were significantly higher in patients with orthostatic syncope than healthy controls, and were particularly severe in those with POTS. Fatigue associated with orthostatic syncope disorders spanned multiple domains, with each dimension contributing equally to increased fatigue. “Brain fog” was an important symptom of POTS, negatively affecting productivity and cognition. Finally, fatigue was negatively associated with mental health in patients with POTS. Conclusion In conditions of orthostatic syncope, fatigue is prevalent and debilitating, especially in patients with POTS. The consideration of fatigue in patients with orthostatic disorders is essential to improve diagnosis and management of symptoms, thus improving quality of life for affected individuals.

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