Background : This study aimed to quantify the 2-year mediating effects of physical activity (PA) and eating behavior (EB) on socioeconomic and sex inequalities in quality of life (QoL) among French adolescents. Methods : Adolescents from a 2-year school-based trial were included. PA and EB were assessed at baseline, 1 year, and 2 years using the International Physical Activity Questionnaire and an eating habits questionnaire, respectively. QoL was measured at 2 years using the Duke Health Profile questionnaire. The mediating effect of adherence to PA and EB guidelines in the associations between socioeconomic status or sex and QoL was analyzed with a counterfactual method. Results : Among the 3562 included adolescents (mean age, 15.2 [0.6] y), being a boy and having a high socioeconomic status was associated with high QoL. Differences in QoL by socioeconomic status were mediated by adherence to guidelines for PA (up to 10.2%) and EB (up to 8.8%), and differences in QoL by sex were predominantly mediated by adherence to guidelines for PA (up to 163.8%). Conclusions : Policies, programs, and interventions designed to reduce socioeconomic and sex inequalities in QoL among adolescents could use PA and EB as leverage.