Abstract Background The following protocol pertains to a pioneer study, aiming to investigate how weather sensitivity and walking in different environments affects the psychophysiological responses to the stress of individuals with coronary artery disease (CAD) during rehabilitation (WE_SENSE_THE_NATURE). This randomised control trial will provide fresh insight on the influence of the environmental exposure in CAD patients, as it is seldom investigated in association to the disease. Additionally, findings on the link between personality traits and cognitive functions (especially cognitive flexibility), and weather sensitivity may help reveal a fine-grained perspective on the treatment possibilities for individuals with CAD at risk to stress-vulnerability. Methods The proposed protocol is for a randomised control trial among individuals attending a cardiac rehabilitation program. We aim to recruit 164 individuals, collecting information related to demographic characteristics, weather sensitivity, functional capacity, personality traits, subjective mental health status, cognitive function, and basal cortisol level of participating individuals. Basal cortisol level refers to cortisol concentration in saliva and will be tested in the morning and the afternoon prior to the day of the experiment. After baseline measurements, the patients will be randomly assigned to either walking outdoors or walking indoors. All measures and their sequential order will remain the same within each group, while the treatment condition (i.e., walking environment) will vary between groups. On the day of the experiment, hemodynamic parameters (assessed via 6-hour blood pressure measurements), stress level (consisting of assessments of cortisol level), and mood (assessed using visual analogues scale) will be registered. Cold stress test will be administered to evaluate the effect of walking in different environments. Discussion The outcomes of this study may have direct clinical applications for the use of different types of exercise environments in cardiac rehabilitation programs. Awareness about the potential influence of weather sensitivity on the psychophysiological reactions to stress in individuals with CAD may contribute to a timely planning and implementation of actions leading to improved medical care services and preventive measures, especially considering the expected weather oscillations and extreme weather events due to unfolding of the climate change. Trial registration This protocol has been retrospectively registered in ClinicalTrials.gov with identifier code: NCT06139705 on November 20, 2023.