The relationship between adolescents' use of video games and their well-being is controversial and largely unexplored during the COVID -19 pandemic. This study examined the association between adolescent video game use and well-being during a nationwide lockdown (March-May 2020) and investigated whether this association was mediated by emotional self-efficacy and moderated by positive coping. The study involved 168 Italian adolescents aged 14-19 years (M = 16.6 years, SD = 1.6). Data were collected through an anonymous online questionnaire. Moderated mediation analysis showed that playing video games was indirectly associated with lower health complaints and higher affective well-being by mediating emotional self-efficacy. In addition, positive coping was found to moderate the relationship between video game use and emotional self-efficacy. Results indicate that both emotional self-efficacy and positive coping enabled adolescents to benefit from playing video games in terms of individual well-being during home confinement.