Objective To investigate the effects of chronic restraint stress for 28 days during the day and night on the mood and cognitive-like behavior of male and female ICR mice, so as to provide a basis for the selection of sex and restraint period in experimental animals in the chronic restraint stress model. Methods ?A total of 72 male and half ICR mice were divided into 6 groups: male blank control group, male daytime restraint group, male nighttime restraint group, female blank control group, female daytime restraint group, and female nighttime restraint group. Except for the blank control group, the other groups were bound for 10 h every day and continuously restrained for 28 days to establish a chronic restraint stress model. The emotional and cognitive behaviors induced by restraint in male and female ICR mice at different times were observed by empty field experiment, Y maze experiment, novel inhibition feeding experiment, elevated cross maze experiment, tail suspension experiment, forced swimming experiment, and dark avoidance experiment. Results In the tail suspension experiment, the immobility time of the male mouse in the daytime restraint group was significantly increased compared with that in the blank group (P<0.05). In the forced swimming experiment, the immobility time of the daytime and nocturnal restraint groups of male mice was significantly increased compared with that of the blank group (P<0.05). In the novelty inhibition feeding experiment, there was no significant difference between the daytime binding group and the blank group, and the feeding latency of the nighttime binding group was significantly longer than that of the blank group (P<0.05) and significantly longer than that of the daytime binding group (P<0.05), and the feeding latency of female mice was significantly longer than that of males during nocturnal binding (P<0.05). In the empty field experiment, the central zone time and central zone time compared with the male blank group were significantly decreased compared with the blank group (P<0.05), the central zone time and central zone time compared with the blank zone were significantly decreased compared with the blank group in the female mice (P<0.05), and the central zone time and central zone compared with the margin zone of the female mouse blank group were significantly increased compared with the male blank group (P<0.05). There was no significant difference between the groups in the elevated cross maze experiment and the Y maze experiment. In the dark avoidance experiment, there was no significant difference between the dark latency of the daytime restraint group and that of the blank group, and the darkness latency of the nighttime restraint group was significantly shortened compared with that of the blank group (P<0.05). Conclusions Male mice exhibit depression after 28 days of chronic restraint stress during the daytime. After 28 days of chronic restraint stress, female mice were prone to anxiety. Learning and memory impairment occurred in male mice after 28 days of chronic restraint stress during the night period.