Natural ventilation has become one of the most effective and sustainable strategies to address COVID-19 in confined spaces. Air intake through windows and other openings improves the Indoor Air Quality (IAQ) of a classroom, decreases the likelihood of respiratory disease transmission with an adequate social distance of about 1.5 m and is affordable in terms of energy consumption. In this study, a comparison of CO2 concentration, wind speed, number of people, type of ventilation and window surfaces of a school in a Mediterranean climate is carried out for 4 different cases of opening. For this purpose, CO2 levels were measured in different classrooms with different window openings (33%, 67%, 81%, 81%). (33%, 67%, 81% and 100% respectively). In addition, three types of ventilation (cross ventilation, partial cross ventilation and multidirectional ventilation) were analyzed in a time period between February and March 2021. The results show an interaction between CO2 levels and the type of ventilation. Thus, the fact that the window surface is a critical factor in reducing CO2 concentrations was determined, considering that the distance between students was approximately 1.5 m. Therefore, the orientation of buildings towards the predominant wind direction and the Window to Floor Ratio (WFR) should be reconsidered in new constructions. Keywords: natural ventilation, indoor air quality, carbon dioxide (CO2) concentration, school, WFR.