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. We argue in the present research that the dark side of such office designs may be explained by a general feeling of de-humanization, i.e. a re-emerging concept that has recently been operationalized in the field of organizational psychology. Adopting a mixed methods approach, we first administrated a quantitative survey to 534 employees working in a variety of office designs. Results show that the three specific office designs under study (i.e., cell, open-plan, and flex offices) were associated with different levels of de-humanization and that this feeling of de-humanization mediates their impact on employees’ psychological strains, job satisfaction, affective organizational commitment, extra-role performance, and turnover intentions. These findings led us to conduct, as a second step, 17 in-depth interviews with employees facing these various office designs in order to investigate how they resent their office designs and why they experience the feeling of de-humanization. The analysis of this qualitative material reveals three main mechanisms in the development of the feeling of de-humanization experienced as a consequence of office designs: a triple feeling of dispossession (of space, voice and professional mastery), a feeling of abandon and an injunction to adopt a modern behavior. The implications of our results are discussed both at the theoretical and practical levels.