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Patients with neurological impairments often experience physical deconditioning, resulting in reduced fitness and health. Powered exoskeleton training may be a successful method to combat physical deconditioning and its comorbidities, providing patients with a valuable and novel experience. This systematic review aimed to conduct a search of relevant literature, to examine the effects of powered exoskeleton training on cardiovascular function and gait performance. Two electronic database searches were performed (2 April 2020 to 12 February 2021) and manual reference list searches of relevant manuscripts were completed. Studies meeting the inclusion criteria were systematically reviewed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. n = 63 relevant titles were highlighed; two further titles were identified through manual reference list searches. Following analysis n = 23 studies were included. Data extraction details included; sample size, age, gender, injury, the exoskeleton used, intervention duration, weekly sessions, total sessions, session duration and outcome measures. Results indicated that exoskeleton gait training elevated energy expenditure greater than wheelchair propulsion and improved gait function. Patients exercised at a moderate-intensity. Powered exoskeletons may increase energy expenditure to a similar level as non-exoskeleton walking, which may improve cardiovascular function more effectively than wheelchair propulsion alone.