Background: To date, there is a considerable amount of evidence on the positive effects of exposure to natural environments on mental health and wellbeing. This field of research does not sit within medical or health care disciplines and it has been slow to penetrate them. Thus, this study aims to explore the potential for enhancing the effectiveness of an intervention by combining it with exposure to a natural environment on stress -related symptoms. Methods: Participants (n=99) were randomly assigned to a weekly one -hour brief mindfulness -based stress reduction (MBSR) in one of three different environments (i.e., natural outdoor, built outdoor and indoor setting) over a six -week period. They were asked to complete the questions in depression anxiety stress scales (DASS-21) four times during the research period at before MBSR (T0), during MBSR (T1), after MBSR (T2) and one -month follow-up (T3). The participants who completed at least five MBSR sessions were invited to donate hair samples to measure the physiological changes of stress levels. Results: The results of DASS-21 showed that all three groups experienced changes in levels of depression, anxiety and stress during the intervention. In particular, participants' depression and stress levels were more decreased in the natural outdoor environment, compared to other environments. However, no significant differences in hair cortisol concentration (HCC) between the environments were found. Conclusions: This study offers valuable insights into the role of natural environments in the effectiveness of a therapeutic intervention. The findings have applications relevant to clinical settings for the treatment of mental health issues, or where the alleviation of stress, anxiety or pain is a priority. Trial Registration: This study was registered at ClinicalTrials.gov (ID: NCT05451758).