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The purpose of the study is to examine the associations of youth physical activity and screen time with weight status and cardiorespiratory fitness in children and adolescents, separately, utilizing a nationally representative sample. A total of 1,113 participants (692 children aged 6–11 yrs; 422 adolescents aged 12–15 yrs) from the 2012 NHANES National Youth Fitness Survey. Participants completed physical activity and screen time questionnaires, and their body mass index and cardiorespiratory fitness (adolescents only) were assessed. Adolescents completed additional physical activity questions to estimate daily MET minutes. Children not meeting the screen time guideline had 1.69 times the odds of being overweight/obese compared to those meeting the screen time guideline, after adjusting for physical activity and other control variables. Among adolescent, screen time was significantly associated with being overweight/obese (odds ratio = 1.82, 95% confidence interval: 1.06–3.15), but the association attenuated toward the borderline of being significant after controlling for physical activity. Being physically active was positively associated with cardiorespiratory fitness, independent of screen time among adolescents. In joint association analysis, children who did not meet physical activity nor screen time guidelines had 2.52 times higher odds of being overweight/obese than children who met both guidelines. Adolescents who did not meet the screen time guideline had significantly higher odds ratio of being overweight/obese regardless of meeting the physical activity guideline. Meeting the physical activity guideline was also associated with cardiorespiratory fitness regardless of meeting the screen time guideline in adolescents. Screen time is a stronger factor than physical activity in predicting weight status in both children and adolescents, and only physical activity is strongly associated with cardiorespiratory fitness in adolescents. [ABSTRACT FROM AUTHOR]