In a mixed reality (MR) environment that combines the physical objects with the virtual environments, users’ feelings are immersed in the virtual world, while their bodies remain in the physical world. Compared to the purely physical environments, such characteristic has led to some special needs for users’ long-term immersion. However, the deficiency needs that we have to face for long-term immersion still need further research. In this paper, we apply the theory of Maslow’s Hierarchy of Needs (MHN) to guide the design of MR systems for long-term immersion. Taking the normal biological rhythm of human beings as the basic unit (24 hours), we propose the fundamental needs for long-term immersion in Ves through combining the theory of MHN with the special needs of virtual reality (VR). In order to verify whether those needs can satisfy users’ long-term immersion, we design an MR office system for basic operations based on the theory of MHN. A long-term exposure experiment (duration of 8 hours) is designed to evaluate those needs by comparing the results with a physical work environment after a short-term preliminary study. The physiological and psychological effects are tested in both two environments and the deficiency needs for short-term immersion and long-term immersion are also compared. The results showed that the design based on the theory of MHN can support users’ long-term immersion, which means that it can be a guideline for long-term use of MR systems.