Over the past decades, Southern European residential architecture has been typically associated with heavyweight hollow brick masonry and reinforced concrete construction systems; however, more industrialised alternative systems have been gaining a significant market share, such as the light steel framing (LSF). Regardless of the proliferation of LSF buildings, a lack of experimental research studies have been performed on this construction system in terms of the indoor thermal environment and thermal comfort in the Southern European climate context. Moreover, a research gap also exists regarding experimental comparisons with typical brick masonry buildings. The present study focused on this research gap by characterising and comparing the performance of these two construction systems. A long-term experimental campaign was carried out, involving the construction and monitoring of two identical test cells, differing only by construction system. The test cells were located in Portugal and were monitored over an entire year. The results revealed that the LSF experimental test cell presented higher daily indoor air temperature fluctuations, leading to more extreme maximum and minimum values, closely following the outdoor dry bulb temperature variations. The more responsive behaviour was also reflected in the indoor thermal comfort analysis, with the LSF cell presenting slightly worse performance; however, some advantages were also observed regarding the LSF construction system, which could provide benefits during intermittent residential occupation, especially in mild climates, in which overheating is not a major concern.