Adolescents’ daily life has dramatically changed during the COVID-19 era due to the social restrictions that have been imposed, including closures of schools, leisure centers and sport facilities. The purpose of this study was to examine levels of well-being and mood and their relations with physical (in)-activity and eating behaviors in adolescents during a lockdown period in Greece. A total of 950 adolescents (Mean Age = 14.41years ± 1.63) participated in a web-based survey while education was online and organized sport activities were interrupted. Participants showed poor well-being, insufficient physical activity levels and moderate scores of healthy eating behavior. Hierarchical regression analysis showed that, after controlling for the effect of gender and body mass index, increased physical activity and healthier eating behavior predicted better well-being, whereas sedentariness predicted worse well-being. Furthermore, it was revealed that days of physical activity per week was a stronger predictor of well-being than minutes of physical activity per week, and that both in-house and out-of-house physical activity were beneficial. Considering that well-being was below the threshold recommended by the WHO as indicative of possible depressive symptoms, measures to increase physical activity and improve eating behavior should become a priority for communities and policy makers.