The use of low exergy cooling concepts in the built environment can reduce the reliance upon high-quality energy sources. However, the application of such cooling systems can result in whole-body and local discomfort of the occupants. The differences in thermal perception between genders are studied to understand how convective and radiant cooling may impact upon comfort. Physiological and thermal sensation data indicate significant differences between the different experimental cases for each gender. For the prediction of thermal sensation and thermal comfort under non-uniform conditions, the operative temperature only is not sufficient. Combined local factors play an important role in the comfort assessment. For females, the local sensations and skin temperatures of the extremities have a significant influence on whole-body thermal sensation and are therefore important to consider under non-uniform environmental conditions. The results show that existing thermal comfort standards are not suitable for application under non-uniform thermal environments for the assessment of thermal comfort. Local effects, as local skin temperatures, play an important role in the whole-body thermal assessment. Therefore, the operative temperature alone is insufficient for the assessment of thermal comfort.