The fundamental aspiration of new-generation high-performing buildings is to reduce energy use while securing indoor environmental quality conducive to human health and productivity. However, existing frameworks for identifying Key Performance Indicators (KPIs) of buildings are sporadic and limited to a few parameters. Based on two Swiss open-space buildings, this paper demonstrates an economic comparison combining three KPIs: health (represented by sick building syndrome (SBS) symptoms), occupants' productivity (based on the thermal environment and ventilation), and operational energy for heating (based on building simulations using measured inputs). Monetization translated various criteria into the same unit currency and compared them on equal terms. Three scenarios for human- and energy-related performance analysis were actual (considering measured data), standard (using parameters from the national standard), and optimal (maximized productivity). The actual environment in case studies measured in the Fall and Winter seasons was relatively warm, with poor ventilation in one of the two buildings as no mechanical ventilation was on. Therefore, there was some loss of productivity (0.11-0.4%) and SBS symptoms (e.g., dry eyes, fatigue) present in both buildings resulting in up to 2 times the difference between the energy and human costs. The minimum energy costs for the standard scenario indicated that standard settings prioritize energy objectives. Oppositely, energy costs were the highest (47.6-69.6%) in the optimal scenario minimizing the human-related costs but not the weekly SBS symptoms. The analysis presented highlights the conflicting goals when one parameter is prioritized over another one, thus demonstrating the importance of a multi-criteria approach.