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The aim of this study is to experimentally assess the effects of an intervention program through a video game called “Aislados” for the improvement of subjective well-being, mental health and trait emotional intelligence of a sample of adolescents (n = 187). We used well-established measures with appropriate psychometric properties. The study used a quasi-experimental design of pre-test/post-test repeated measurements with a control group. First, a multivariate analysis of variance (MANOVA) and then descriptive analyses and variance analyses (ANOVAs) were carried out by the adolescents randomly assigned to the experimental and control conditions. Then, a multivariate analysis of covariance (MANCOVA) was performed on the study’s variables as a whole. Descriptive and covariance analyses of the post-test scores were carried out (ANCOVAs post-test, co-varying pre-test scores), in order to demonstrate the impact of the program. The effect size was reckoned (Cohen’s d). The results confirm statistically-significant differences in: Health-Related Quality of life, positive affect and mental health. The study provides an effective intervention tool which has been experimentally validated. The overall results allow for emphasizing the importance of the implementation of programs aimed at encouraging social and emotional learning throughout adolescence as protective resources in fostering emotional and behavioral adjustment in adolescents.