It has been reported that more than one fourth of the world’s population suffers from sleep problems. However, there is not a stable and reliable animal model to mimic the persistent and periodic features of sleep disorders, and correspondingly, the feasibility and effectiveness of repeated behavioral tests remains to be determined. In the present study, we repetitively, and intermittently, treated mice with 3 days and 7 days of paradoxical sleep deprivation (SD), using the modified multiple small-platforms-over-water method for 3 months. The behavioral results suggested that repeated open field and Y-maze tests are able to successfully detect anxiety-like behaviors and working memory dysfunction of the model mice. The Morris water maze test is not suitable for evaluating spatial learning ability following SD because the long-term utilization of the flower-pot method increases the familiarity of mice with the water environment. Moreover, neuroinflammation, microglial activation and neuronal apoptosis were observed in the hippocampus of model mice even recovery for 3 weeks later. This animal model and corresponding behavioral evaluation method will help to explore the pathogenesis and therapeutic strategies of chronic sleep disorders.