Objective: To investigate the impact of COVID-19 infection and health related behaviors on the health related quality of life of children and adolescents aged 8-15 years in Nanjing, so as to provide a theoretical basis for improving HRQoL in children and adolescents. Methods: From December 2022 to January 2023, a total of 2 398 students aged 8-15 years from the third grade of primary school to junior middle school in Nanjing were selected by multistage random cluster sampling. The 3 level EuroQol 5 dimension Questionnaire Youth Vension (EQ-5D-Y-3L) was completed by the respondents on their own, and the parents assisted in completing the rest of the questionnaire. Results: The EuroQol-index(EQ-index) and Visual Analogue Scale (VAS) scores of being infected individuals were lower than those of uninfected and previously infected ( P <0.05). The proportion of being infected individuals reporting difficulty on "Pain/Discomfort" was higher than that of uninfected and previously infected individuals, and the proportion of reporting difficulty on "Mobility" was also higher than that of uninfected individuals ( P <0.05). Lack of parental companionship( OR=10.19, 95%CI =3.12-33.22), irregular breakfast consumption ( OR=10.63, 95%CI =3.20-35.25), and excessive screen time ( OR=8.24, 95%CI =3.02-22.51) increased the risk of difficulty on "Mobility" in being infected individuals ( P <0.05). Irregular breakfast consumption ( OR=1.93, 95%CI =1.31-2.84) and consumption of sweetened beverages and snacks (OR=1.56, 95%CI =1.17-2.10) increased the risk of having lower EQ index in previously infected individuals compared to uninfected individuals. Furthermore, consumption of sweetened beverages and snacks ( OR=1.57, 95%CI =1.21-2.05) and excessive screen time ( OR=1.49, 95%CI =1.12-1.98) also increased the risk of VAS scores being lower in previously infected individuals compared to uninfected individuals ( P <0.05). Conclusion The COVID-19 infection impairs HRQoL, and unhealthy behaviors deteriorate its negative impact. Healthy behaviors and lifestyles should be advocated to reduce the impact of COVID-19 infection on HRQoL.