Study Objectives: Investigate whether a realistic "dose" of shortened sleep, relative to a well-rested state, causes a decline in adolescents' learning and an increase in inattentive and sleepy behaviors in a simulated classroom setting. Methods: Eighty-seven healthy 14.0- to 16.9-year olds underwent a 3-week sleep manipulation protocol, including two 5-night sleep manipulation conditions presented in a randomly counterbalanced within-subjects cross-over design. Wake time was held constant. Bedtimes were set to induce Short Sleep (SS; 6.5 hours in bed) versus Healthy Sleep (HS; 10 hours in bed). During the morning at the end of each condition, participants underwent a simulated classroom procedure in which they viewed lecture-based educational videotapes and completed relevant quizzes. Their behaviors in the simulated classroom were later coded by condition-blind raters for evidence of inattention and sleepiness. Results: Adolescents had a longer average sleep period during HS (9.1 hours) than SS (6.5 hours). Compared to scores during HS, adolescents scored significantly lower on the quiz, showed more behaviors suggestive of inattention and sleepiness in the simulated classroom, and were reported by adolescents themselves and by their parents to be more inattentive and sleepy during SS. However, the impact of the manipulation on quiz scores was not mediated by changes in attention or sleepiness. Conclusions: Although effect sizes were modest, these findings suggest that previously-reported correlations between sleep duration and academic performance reflect true cause-effect relationships. Findings add to the growing evidence that the chronically shortened sleep experienced by many adolescents on school nights adversely impacts their functioning and health.