Background: The negative association of quality of life (QoL) and negative life evens (NLEs) among adolescents has been proved by cross-sectional studies, without exploring sex differences. This study aimed to explore the longitudinal associations between QoL and NLEs among adolescents during novel coronavirus disease 2019 (COVID-19) pandemic and whether there are sex or age differences. Methods: A stratified cluster sampling was used to select 1421 students in primary school and middle school in Chongqing, China. From November 2020 (T0) to December 2021 (T2), the Adolescent Self-Rating Life Events Checklist and the Adolescent Quality of Life Scale were used to collect 3 waves of data. The correlations between study variables were conducted by the Pearson correlation analyses. The direction and strength of the longitudinal associations were analyzed using cross-lagged panel analyses. Results: Results showed significant changes in both variables during COVID-19 pandemic (P < 0.001). Cross-sectional analyses showed stable negative correlations between NLEs and QoL stratified by sex or by age (P < 0.001). Sex and age differences in longitudinal relationships were shown by cross-lagged panel analyses. For males, NLEs had a short-term bi-directional association with QoL [¢ A-D = ¹(0.091-0.340), P < 0.05]; for females, QoL had a short-term correlation with NLEs [¢ A = ¹0.119), ¢ C = ¹0.109), P < 0.001]. In the youngest age group, NLEs had a short-term bi-directional correlation with QoL [¢ A-D = ¹(0.098-0.428), P < 0.05]. There was a short-term association between total QoL and NLEs among students except the 14³15 year group [¢ A = ¹(0.071-0.149), ¢ C = ¹(0.086-0.119), P < 0.05], the long-term association between total QoL and NLEs was only significant in adolescents aged 14³15 years (¢ E = ¹0.132, P < 0.05). The strength of NLEs was slightly higher than that of total QoL, but lower than that of QoL in each dimension. Conclusion: There were negative longitudinal relationships between NLEs and QoL during COVID-19 pandemic, and the strength of the associations varied across sex or age. Strengthening QoL in different dimensions may be a promising way to reduce NLEs during the pandemic among adolescents, and interventions should be tailored according different sex and ages.