Sleep may play a role in overweight and obesity in adolescents. The objective of this study is to investigate the relationships between sleep duration and timing and overweight and obesity status in adolescents, with a special emphasis on weekday-weekend difference in sleep characteristics as well as sex-specific relationships. We examined 1,254 U.S. adolescents (12-17 years) self-reported sleep duration, timing, weekday-weekend differences in duration and timing in relation to overweight and obesity. We found an inverse association between sleep duration and overweight and obesity. Compared to 8-9 h of sleep, short sleep (< 7 h) on weekdays was associated with higher odds of overweight and obesity [Odds ratio (95% confidence interval), 1.73 (1.00, 2.97)] in the overall population, while long sleep (10+ h) on weekends was associated with lower odds, but only in males [0.56 (0.34, 0.92)]. We also found that a larger weekday-weekend difference in sleep duration was associated with overweight and obesity in females, but not in males. Specifically, the odds of overweight and obesity were significantly higher among females reporting longer sleep on weekends than weekdays by ≥ 2 h [2.31 (1.15, 4.63)] when compared to those reporting little weekday-weekend differences. Sleep timing, or weekday-weekend differences in sleep timing, were not associated with overweight and obesity in the overall population, although we found suggestive evidence linking later weekend sleep with overweight and obesity in females. Our findings support a role of sleep in adolescent obesity and suggest sex-differences in this relationship that warrant future studies.