This paper investigates the impact of climate change on comfort and energy performance in offices in relation to the influence of building design and occupants. It focuses on a typical cellular office room in the context of Athens, Greece, as input for a parametric study using the building simulation software EnergyPlus. Three different building design variations are combined with two different occupant scenarios and 4 different weather data sets for IPCC climate change scenario A2. For naturally ventilated buildings adaptive thermal comfort is evaluated according to ASHRAE Standard 55 and EN 15251. For mixed mode context evaluation is focused on greenhouse gas emissions and peak heating / cooling loads. Results indicate significant impact of the climate change on thermal comfort, and deviations between both comfort models. Comparing climate change, building design and occupant scenarios indicates that building design is the predominant influence on thermal comfort, whereas occupants are the predominant influence on greenhouse gas emissions