Objective To observe the effects of high-altitude hypoxia exposure for 4 weeks on neuroethology in mice. Methods C57BL/6J mice were randomly divided into two groups: control group and hypobaric hypoxia group. Mice in the hypobaric hypoxia group were put in a hypobaric hypoxia chamber that simulated an altitude of 6000 m for 4 weeks of exposure. Body weight was measured once a week. An open field test, tail-suspension test, and elevated plus maze test were used to detect changes to the emotional behaviors of mice. A weight-bearing swimming test and rotarod test were used to detect changes in the physical fitness of the mice. A new object recognition test, Y maze test, and Morris water maze test were used to detect changes to cognition, learning, and memory. Results Compared with the weights of the control group, the weight of mice exposed to hypoxia decreased significantly in the first week(P<0. 001). The open field test showed that hypoxia exposure had no effect on the spontaneous activities of mice, and the tail-suspension and elevated plus maze tests showed that there was no obvious negative emotion in hypoxia-exposed mice. The weight-bearing swimming test showed that the exhaustion latency of mice was shortened after hypoxia (P< 0. 01), but there was no explore new things and new environments decreased, and the recognition index decreased after hypoxia (P< 0. 05). Working memory decreased significantly in the Y maze test after hypoxia (P<0. 05), and there was no difference in spatial learning or memory between the two groups. Conclusions Four weeks of exposure to simulated high-altitude hypoxia affected many neuroethological indexes in the mice, among which exhaustion latency in the exhaustion swimming test, the cognitive index in the new object recognition test, and the percentage entering the new open arm in the Y maze test were the most sensitive indexes.