Indoor air quality (IAQ) and energy consumption (Q) are well-known building estimators, but they are used separately. Energy consumption is used during the design stage, while IAQ is used during operation. The novelty of our approach is that we propose using both estimators simultaneously during building operations. The purpose of this study was to find an adaptive ventilation strategy that maintained good indoor air quality with minimal energy consumption. The second novelty of our approach consists of IAQ estimation. While the operation of ventilation systems depends only on the indoor carbon dioxide (CO2) concentration at present, our novel approach uses a more global IAQ index that includes four different air pollutants. Physical models are used for the hourly prediction of the two indices: global IAQ and Q. This study presents a comparative analysis of several ventilation operations strategies: fixed versus adaptive. The main findings show that a decrease in the ventilation rate, na, from 3.5 h−1 to 2.0 h−1 leads to a diminishment in energy consumption of 42.9%, maintaining the global IAQ index under the limited health risk value (VRL). Moreover, an adaptive ventilation strategy of na, maintaining the global IAQ index value under VRL, achieves a further reduction in energy consumption of 72.9%, highlighting its efficiency.