Background: Cognitive impairments as sequelae of brain injury are common and can negatively affect activities of everyday life, participation and quality of life. Thus, finding ways to reduce cognitive impairments and ameliorate their negative impact on everyday life is an important focus of research. Aim: The aim of this pilot study was to analyse the effects of a combination of guided mindfulness and aerobic exercise on cognitive ability and mental fatigue in patients with acquired brain injury (ABI). Design: Pilot study, with a before-after design. Setting: Outpatient. Population: Twenty-one patients suffering from ABI, former patients of three rehabilitation medicine departments. Methods: The intervention comprised a structured combination of guided mindfulness program and outdoor walking, three times/week for 12 weeks. The outcome measures included assessment of information processing speed, working memory, oxygen uptake and self-reported mental fatigue. Results: The main results showed improvements in cognitive abilities related to information processing speed, perceived mental fatigue and physical capacity. Conclusions: A combination of mindfulness and physical activity can increase information processing speed and ameliorate mental fatigue. Further studies are needed to confirm our findings. Clinical Rehabilitation Impact: The combination of guided mindfulness and physical activity shows promise as a treatment modality in rehabilitation of impaired information processing speed and mental fatigue following ABI.