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In a virus pandemic context, buildings ventilation has been recognized as a solution for preventing transmission of the virus in aerosolized form. The impact of the widespread recommendation of window opening and sealing door on ventilation circuits needs to be considered with a multizone approach. We modeled the airflow distribution in a building where people are isolating in a pandemic context, including one infected person. We analyzed the impact of opening the window and sealing the door in the quarantine room on exposures and probability of infection for occupants of the flat and of adjacent flats. In order to study the sensitivity of the results, we tested three ventilation systems: balanced, exhaust‐only, and humidity‐based demand‐controlled, and several window‐ and door‐opening strategies. When the door of the quarantine room is sealed, we observe that opening the window in the quarantine room always results in increased exposure and probability of infection for at least one other occupant, including in neighbors' apartments. When all internal doors are opened, we observe moderate impacts, with rather an increase of exposure of the occupants of the same apartments and of their probability of infection, and a decrease for the occupants located in other apartments. Based on the analysis on the airflows distribution in this case study, we conclude that sealing the internal door has more influence than opening the window of the quarantine room, whatever the ventilation system. We observe that this widespread recommendation to open the window of a quarantine room and to seal the door is based on the consideration of a single zone model. We illustrate the importance of moving from such a single zone approach to a multizone approach for quantifying ventilation and airing impacts in multizone buildings as residences in order to prevent epidemics of viruses such as SARS‐CoV‐2. It highlights the need of air leakage databases. [ABSTRACT FROM AUTHOR]