The air conditioning applications in mosques are considered as one of the important HVAC applications, which flow pattern and thermal comfort depend on the behavior of the airflow, the distributions of temperatures and relative humidity and concentration of CO2 due to high occupancy load of people. The paper is devoted to numerically investigate the influence of location and number of ventilation and air conditioning supply and extracts openings on airflow properties. The example shown here is Al-Masa’a between Al-Safa and Al-Marwa hills inside Al-Haram mosque located at Makkah-Saudi Arabia. The work focuses on airflow, thermal behavior and CO2 dispersion where large number of people. Five different cases for change in location supply-extract air are studied to reveal the impact of changing the location on the overall comfort levels for people. The performance of the air conditioning system is characterized by airflow patterns, temperature, relative humidity contours and CO2 concentration as well as the most commonly used comfort parameters PMV and PPD based on Fanger’s model. This is the main target during the present work.