This report presents the methodological approach and key findings of the eCOMBINE project (“Interaction between energy use, COMfort, Behaviour, and INdoor Environment in Office Buildings”). In this project, we develop an integrated approach to study the cause-effect relationships between occupant perception and behaviour, combined multi-domain indoor environmental factors (thermal, IAQ, visual and acoustic), and energy use. The eCOMBINE project relies on a mixed experimental approach that combines environmental measurements in the open-space office space with subjective responses from the building occupants. The eCOMBINE framework was applied to two Swiss pilot case studies located in Lausanne (Building A) and Geneva (Building B) with 13 and 31 participants, respectively. Based on data collected in these two open space offices, the outcomes of this work reveal relationships between global environmental stimuli (PART A), multi-domain environmental perceptions in real office settings (PART B), perceived multi-domain motivations behind human-building interactions (PART C), and energy use (PART D). Building simulations with measurement-based input further highlight energy performance gaps between the actual operation (based on real/tracked behaviour of occupants) with respect to recommended simulation input by Swiss standards.