摘要:Objective: Self-efficacy is an essential variable contributing to adolescents' well-being and academic success. The literature on the topic underlines that adolescents with effective metacognitive strategies show high levels of self-efficacy. Furthermore, a recent line of research has focused explicitly on the relationship between self-efficacy and the skills essential to developing adequate abilities to acquire positive behaviors and effectively face life challenges (“life skills”). The relationship between these variables and how it could affect stress perception and quality of life during adolescence are still little investigated and need more research attention. Specifically, this study aimed to investigate the impact of self-efficacy, life skills, and metacognition on stress perception, depressive and anxiety symptoms, and quality of life in a sample of Italian adolescents. Methods: 389 high school students (males = 149; females = 240; age range: 14–19.2, M = 16.61, SD = 1.05) were randomly recruited from five Italian public high schools. The participants completed a battery of five standardized tests between November 2019 and January 2020. The questionnaires assessed five dimensions of social and interpersonal skills (Non-affirmation, Impulsiveness, Narcissism, Social preoccupation, and Stress in social situations), perceived stress, general self-efficacy, metacognition, and quality of life. Data were analyzed using structural equation modeling. Results: Results showed a direct effect of all five dimensions of interpersonal skills on self-efficacy and quality of life (p.001). Furthermore, data confirmed the indirect effect of metacognitive skills on the relationship between all interpersonal skills and the sense of self-efficacy and a partial mediation of metacognition in the relationships with self-efficacy. Conclusions: This study underlines the significant impact of the investigated variables on adolescents' quality of life and stress perception. These findings suggest a need for specific programs to enhance life skills to improve adolescents' mental health and psychological well-being.