This study investigated whether adjusting clothing to remain in neutral thermal comfort at moderately elevated temperature is capable of avoiding negative effects on perceived acute subclinical health symptoms, comfort, and cognitive performance. Two temperatures were examined: 23°C and 27°C. Twelve subjects were able to remain thermally comfortable at both temperatures by adjusting their clothing. They rated the physical environment, their comfort, the intensity of acute subclinical health symptoms, and their mental load, and they performed a number of cognitive tasks. Their physiological reactions were monitored. Their performance of several tasks was significantly worse at 27°C, and they reported increased mental load at this temperature. Skin temperature and humidity and respiration rate were higher, while blood oxygen saturation (SpO2) and pNN50 were lower at this temperature, the latter indicating increased stress. It is inferred that the observed physiological responses were mainly responsible for the negative effects on performance, as the subjects did not indicate any increased intensity of acute subclinical health symptoms although perceived air quality was worse at the higher temperature. The present results suggest that moderately elevated temperatures should be avoided even if thermal comfort can be achieved, as it may lead to reduced performance.