In the domain of building science and architectural design, the immersive virtual environment (IVE) is being commonly adopted due to its convenience and cost-effectiveness, especially for research relevant to occupant behavior in a building indoor environmental control. The goal of this study is to investigate whether such an IVE condition affects an occupant’s thermal sensation and physiological response to ambient conditions differently, as compared to a real indoor environment (IE), even though those two thermal conditions are the same or very similar. A series of human subject experiments using 18 participants was conducted in an environmental chamber. While the thermal conditions were controlled between 20°C and 30°C in each environment, respectively, the subjects were asked to periodically report their thermal sensations on their whole and local body areas. Their heart rates, as a physiological response variable, were also continuously measured. During the test, other environmental variables, including lighting, air, acoustic and visual conditions were consistently maintained. The result of the experiment revealed that overall thermal sensations on the whole and local body areas showed some significant differences between the IE and IVE conditions during the same thermal conditions. Also, the heart rate difference between the two environmental conditions was statistically significant at every thermal sensation level. These findings support the idea that significant physiological response differences might be affected by the IVE condition. However, this inconsistency could also be attributed to the human factor of each subject, such as gender and BMI.