Abstract Introduction Short sleep is often associated with worse academic outcomes, but it remains unknown whether this relationship is causal. In addition, many students perceive that cutting back on sleep is necessary for successful performance in rigorous and intimidating courses, such as organic chemistry. In the current work, we experimentally tested whether acute sleep restriction affected organic chemistry learning outcomes. Methods Participants were 60 undergraduate students who had not previously taken organic chemistry. They maintained a sleep diary for seven days and then completed an overnight session that included polysomnography (PSG) monitoring. Participants were randomly assigned to go to bed at either 10:30pm (normal sleep) or 1:30am (sleep restriction). The next morning, all participants were woken up at approximately 7am and completed a virtual lecture on organic chemistry. In one segment, the lecture was self-paced; in the other segment, the lecture was set to advance automatically at a speeded pace. Following the lecture, participants completed a 50-item test over the studied material. Results The conditions were similar in age, gender, race/ethnicity, chemistry intimidation, chronotype, prior sleep, and fluid intelligence (ps > .30). The bedtime manipulation successfully decreased total sleep time from 454.10 (47.90) minutes to 300.93 (37.23) minutes (p<.001), by decreasing time spent in REM and N2 (ps<.01; no changes to N1 or N3, ps>.05). Sleep restriction significantly altered stress levels during the test (p<.05), but not test performance (p>.10). Organic chemistry test performance was lower after a speeded lecture than a self-paced lecture, F(1, 57) = 15.649, p < .001, though this pattern did not interact with sleep condition (ps>.10). Students who were more intimidated by chemistry (at baseline) performed more poorly on the speeded section (r=-.36, p<.01), but just as well on the self-paced section (r=-.09, p=.51), and these patterns were not moderated by sleep duration. Conclusion Students who are intimidated by organic chemistry learning can overcome these barriers via self-paced learning, even when they have been acutely sleep restricted. Support (if any) This work was supported by the National Science Foundation (1943323 and 1920730).