Natural cross ventilation has become one of the most effective and sustainable strategies to address respiratory pandemics in confined spaces. Air intake through windows, doors and other openings improves the Indoor Air Quality (IAQ) of a classroom, decreases the likelihood of respiratory disease transmission when social distancing of about 1.5 m is observed, and is affordable in terms of energy consumption. In this study, a comparison between types of cross ventilation from CO2 concentration, number of people and window and door surfaces of a school in a Mediterranean climate is carried out for 3 different cases of openings. For this purpose, CO2 levels were measured in two similar and annexed classrooms with different window and door openings (0%, 33% y 66%) with 2 loading and unloading sequences. Two types of cross ventilation were analyzed: cross ventilation with window and door in the same direction or direct (CDIR), and diagonal cross ventilation (CDIA), in a time period of 3 h. in December 2022. The results show an interaction between CO2 levels and the type of ventilation. Diagonal cross ventilation was more effective in terms of air renewal (ACH) than direct ventilation, in smaller opening ranges (33%), with direct cross ventilation being more effective globally and in larger opening ranges (66%), under the conditions of this case study. Keywords: natural ventilation; cross ventilation; indoor air quality; carbon dioxide (CO2) concentration; classroom.