Objective To investigate the effects of chronic restraint stress for 28 days (day and night) on mood and cognitive-like behavior in male and female ICR mice, to provide a basis for the selection of sex and restraint period in chronic restraint stress model animals. Methods A total of 72 male and female (1 ∶ 1) ICR mice were divided into six groups: male control, daytime restraint, and nighttime restraint groups, and female control, daytime restraint, and nighttime restraint groups. Mice in all but the control groups were bound for 10 h / d and restrained continuously for 28 days to establish a chronic restraint stress model. The emotional and cognitive behaviors induced by restraint in male and female mice at different times were observed by open field, Y maze, novel inhibition feeding, elevated cross maze, tail suspension, forced swimming, and dark-avoidance experiments. Results In the tail suspension experiment, the immobility time of male mice in the daytime restraint group was significantly increased compared with that in the control group ( P<0. 05), and the immobility times of male mice in the daytime and nighttime restraint groups were also significantly increased in the forced swimming experiment, compared with those in the control group (P<0. 05). There was no significant difference between the female daytime restraint and female control groups in the novelty inhibition feeding experiment, but the feeding latency of the nighttime restraint group was significantly longer than that of the control group (P<0. 05) and the daytime restraint group (P<0. 05). The feeding latency of female mice was significantly longer than that of males during nighttime restraint (P<0. 05). In the open field test, compared with the male control group, the female control group showed a significant decrease in central area time and the ratio of central area time to peripheral area time (P<0. 05). Compared with the female control group, the female daytime restraint group exhibited a significant decrease in central area time and the ratio of central area time to peripheral area time (P<0. 05). There was no significant difference between the groups in the elevated cross maze and Y maze experiments. There was no significant difference in dark latency between the daytime restraint group and the control group, but darkness latency was significantly shorter in the nighttime restraint group compared with those in the control group ( P< 0. 05). When male and female mice were combined, the immobility time in the daytime restraint group was significantly increased in the tail suspension experiment (P<0. 05), the immobility times of mice in the daytime and nighttime restraint groups were significantly increased in the forced swimming experiment ( P<0. 01, P<0. 05), and the central zone time and the ratio of central area time to peripheral area time of daytime restraint mice were significantly shorter compared with those in the control group (P<0. 05, P<0. 01). There was no significant difference in the central zone time and the ratio of central area time to peripheral area time in the nighttime restraint groups, and no significant difference in average speed or total distance between the daytime and nighttime restraint groups. Conclusions Male mice exhibited depression after 28 d of chronic restraint stress during the daytime, while female mice were prone to anxiety after 28 d of chronic restraint stress. Male mice experienced learning and memory impairment after 28 d of chronic restraint stress during the night.