Recent research on flexible office designs have shown that open-plan and/or flex offices may not have the expected effects in terms of employees’ productivity, well-being, job satisfaction, organizational commitment, and retention. In this article, we propose to consider that the feeling of de-humanization may explain such dark side of office designs. Adopting a mixed methods approach, we administrated a quantitative survey to 534 employees working in a variety of office designs, and conducted 12 semi-structured interviews among the respondents to the survey in order to investigate how they experienced their office designs, notably in terms of de-humanization. Results showed that the three specific office designs under study (i.e., cell, open-plan, and flex offices) are associated with different levels of de-humanization and that this feeling of de-humanization mediates their impact on employees’ job satisfaction, affective organizational commitment, extra-role performance, psychological strains, and turnover intentions. Interviews’ analysis reveals three main mechanisms in the development of the feeling of de-humanization in such office designs: a triple feeling of dispossession (of space, voice and professional mastery), a feeling of abandon and an injunction to adopt a modern behaviour.