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In Poland and other countries in Central Europe, residential buildings from the second half of the 20th century dominate, which have recently undergone deep thermomodernisation. Research on the retrofitting of residential buildings has focused mainly on energy efficiency, with only a few studies on indoor air quality. The aim of this study was to present a comparative analysis of the impact of five ventilation scenarios (three natural and two mechanical) on CO2 concentration and energy demand for heating and ventilation in residential spaces of a multi-family building located in Poland. The analyses were based on the results of building performance co-simulation using the EnergyPlus and CONTAM programs carried out under dynamic conditions with a 5 min time step for the entire heating season. The calculations took into account the instantaneous occupancy variability of twenty apartments. In the buildings equipped with new tight windows, the natural ventilation system provided extremely low air exchange (on average 0.1 h−1) and poor indoor air quality (average CO2 concentration at the level of 2500 ppm). Opening windows to ventilate the rooms generated a multiple increase (up to 8 times) in heating demand during these periods, but average CO2 concentration was on the level of 930 ppm. The use of mechanical ventilation was profitable both in terms of energy savings (at the level of 50%) and improvement in the indoor air. [ABSTRACT FROM AUTHOR]