<p>High levels of life satisfaction have important positive implications for the development of adolescents. Despite studies that have examined factors that may favour life satisfaction at these ages, researchers have described a lack of research on this subject using both prospective designs and samples of adolescents. Given that gratitude has been shown to be one of the resources that fosters well-being and health, this study sought to delve into the possible underlying mechanisms in the relationship between gratitude and life satisfaction in adolescents. To do so, based on two theoretical hypotheses, we examined the role of two possible mediators in this relationship: positive affect (positive affect hypothesis) and adaptive cognitive emotion regulation (CER) strategies (coping hypothesis). A sample of 983 students (12–18 years old) participated in this two-wave study. At Time 1 they completed two questionnaire measuring gratitude and life satisfaction. At Time 2 (16 weeks later) participants completed three questionnaires assessing positive affect, adaptive CER strategies, and life satisfaction. The results showed that gratitude had an association on life satisfaction over time. Moreover, according to the positive affect and coping hypotheses, both positive affect and adaptive CER strategies mediated the association between gratitude and life satisfaction over time, after controlling life satisfaction (Time 1). These findings provide a better understanding of the mechanisms underlying the relationship between gratitude and life satisfaction in adolescents. They also suggest the importance of health and well-being benefits of training this resource at these ages.</p>