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Occupant comfort expectations vary across different global locations. However, research efforts have primarily focused on the global north, mainly Europe and North America, limiting our understanding of comfort perceptions in alternative contexts. To address this, an experimental study was conducted in two test rooms, one in a cold climate (Montreal, Canada - ASHRAE Climate Zone 6) and the other in a hot climate (Cairo, Egypt - ASHRAE Climate Zone 2B). The study aimed to deepen our understanding of the intricate relationship between location-specific factors and lighting, thermal comfort, as well as human physiological responses. To achieve this, the experiment investigated the influence of artificial lighting with different Correlated Color Temperature (CCT) on occupant thermal responses, considering both perceptual and physiological aspects, within these contrasting climate zones. A comparative analysis was conducted to evaluate outcomes, focusing on discrepancies in potential cross-effects between visual and thermal comfort domains and variations in physiological indicators like heart rate variability and skin temperature. Results revealed significant differences between the two laboratories’ observed thermal comfort responses. Additionally, significant distinctions were observed between the parameters with neutral light exposure and the cool/warm light conditions. These findings offer valuable insights for practitioners and researchers in developing location-specific guidelines and strategies to create comfortable indoor environments that cater to occupants’ unique expectations in diverse climatic contexts. By shedding light on the impact of location-specific variables and the interplay between visual and thermal comfort, this study contributes to a deeper understanding of occupant comfort considerations, facilitating the creation of more comfortable and optimized indoor spaces, particularly in regions with varying climatic conditions.