The study aimed to quantify both the concurrent and the after effects of the exposure to a short-term crowding- episode in a well-supportive indoor physical setting on a bus, in order to estimate the impact of well-suited physical environment on health and emotional well-being. 40 participants were asked to simulate a 10 minutes-journey on a bus in immersive virtual environments, while multi-methodological data were collected (i.e., subjective measures, physiological responses, and cognitive performance). The subjects were randomly assigned to one of the three experimental conditions, where social density and the presence of well-suited physical elements were manipulated. Results revealed that experiencing a short episode of crowding on the bus (i.e., 10 min.) is sufficient to determine a significant increase in physiological activation (i.e., SCL) as well as to decrease the passengers’ quality of post-exposure experience (i.e., perceived stress); and that providing a well-designed setting layout significantly buffers the aversive consequences of commuting crowding. Mixed results were obtained regarding the low-density condition, in terms of concurrent sympathetic responses (i.e., SCL), and post-exposure cognitive performance (i.e., Color Stroop Task); future research will be needed to untangle these findings. Investigating the direct effects of crowding on human health and well-being, and quantifying the impact of adopting effective coping strategies supported by the physical setting on optimum functioning are crucial issues to be addressed, due to their important implications for both research and practice on healthy environments.