The intensive use of air conditioning systems, primarily refrigerating, to promote thermal comfort in countries such as Brazil (a hot climate country) is changing the electrical energy consumption patterns and peak demand. Even with the increased number of appliances, we must learn to consume less energy to achieve similar outcomes with higher energy efficiency. Consequently, exergy analysis is used to evaluate the quality of these energy conversion systems. Four computational human thermal models were used to assess thermal comfort conditions: one man wearing lighter clothing, one man wearing traditional office clothing, and two women in the two types of clothing. We chose these four models since the body composition and basal metabolism rates for males and females differ. In addition, the insulation of clothes influences the temperature of the thermal environment, leading to a significantly lower percentage of people being unsatisfied, from 12.8% to values close to 5%. The outputs of these occupants are used as inputs for a computational model of the room to calculate its associated thermal loads and evaluate different temperature setpoints and their effects on thermal comfort and energy consumption. Results indicate that environmental temperatures above 24 ∘C and below 26 ∘C may lead to thermal comfort conditions, depending on the occupants’ clothing. Clothing would represent a thermal resistance of 0.7 CLO for men and women (when in the luteal phase of the menstrual cycle) and 0.8 CLO for women in the follicular phase when the environment is at 25 ∘C. Therefore, there is a significant reduction in the compression power of the central cooling system by about 2.2% compared to 24 ∘C and around 8% compared to ambient temperatures around 21 ∘C.