Human health and well-being have gained growing attention in the societal debate as well as in research. It is widely acknowledged that employees’ health and well-being contribute to a decent work environment which can positively contribute to economic benefits for the employers, the social-welfare and health system as well as the building owners. However, the office environment is complex and constitutes of various factors affecting employees’ health and well-being, for example, indoor climate, architectural design, and social work environment. Therefore, this paper will focus on indoor environmental quality (IEQ) and workplace design, and their influence on employees’ health and work performance. A multi-disciplinary approach is developed integrating the subjective survey, semi-structured interview, and physical measurement for an in-depth investigation of the physical office environment and employees’ self-reported health and work performance. A large office building with BREEAM certification has been studied at the end of summer in 2019. In total, 160 employees were involved by an online-based survey and individual interview and workshop. The main aspects of IEQ were measured, including the thermal environment, air quality, acoustic and lighting. The correlations between IEQ and workspace design factors and 5-symptom based self-reported health and self-reported work performance concerning self-evaluation and leader’s feedback were studied. Results show that physical office environment shows a large association with self-reported health and self-reported work performance. IEQ factors of air quality and relative humidity are significantly correlated with PSI. Size of individual workspace and aesthetic appearance of the office gain the highest correlation with self-reported health status among the factors of workspace design. Noise and artificial lights are studied to be significantly associated with work performance, and distance between work desks is largely associated with work performance. Considering the needs of employees on the physical office environment, air temperature, air quality and availability to work concentrated still underperform but perceived as highly important by the employees. The study made efforts to study the complex factors existing in the office environment with a multi-disciplinary approach, which can be utilized in other case studies to evaluate office environment and identify the key factors. Thus, the study made it possible to review and compare the influence of physical environment factors affecting employees’ health and well-being. The data collected will contribute to an office database which is under development by the authors.