COVID-19 has created significant concern surrounding the impact of pandemic lockdown on mental health. While the pandemic lockdown can be distressing, times of crisis can also provide people with the opportunity to think divergently and explore different activities. Novelty seeking, where individuals explore novel and unfamiliarly stimuli and environments, may enhance the creativity of individuals to solve problems in a way that allows them to adjust their emotional responses to stressful situations. This study employs a longitudinal design to investigate changes in novelty seeking and mental health outcomes (namely, stress, anxiety, and depression) before, during, and after COVID-19 pandemic lockdown, among a group of students (final N = 173; Mage = 19.81; SDage = 0.98; 135 females and 38 males) from a university in southeast China. Participants were surveyed at three points: November, 2019 (prior to the COVID-19 pandemic); between February and March, 2020 (during the peak of the pandemic and intense lockdown in China); and between May and June, 2020 (after lockdown had been lifted in China). Cross-sectionally, correlation analysis indicated that greater novelty seeking was associated with lower levels of stress, anxiety, and depression at all three time points. Univariate latent curve modeling (LCM) indicated a growth trajectory in which novelty seeking increased over time and then remained high during the post-lockdown period. Stress, anxiety, and depression all showed V-shaped growth trajectories in which these variables decreased during lockdown, before increasing in the post-lockdown period. Multivariate LCM indicated the growth trajectory for novelty seeking was associated with the growth trajectories for stress, anxiety, and depression. This suggests that the observed decreases in stress, anxiety, and depression during the lockdown period may be attributable to the sample’s observed increase in novelty seeking. These findings are valuable in that they challenge the notion that lockdown measures are inherently detrimental to mental health. The findings indicate the important role of novelty seeking in responding to crises. It may be possible for future public health measures to incorporate the promotion of novelty seeking to help individuals’ respond to stressful situations and maintain good mental health in the face of crises.