BACKGROUND: The authors assessed the impact of lockdown in response to the COVID-19 pandemic on routine-oriented lifestyle behaviors and symptoms of depression, anxiety, and insomnia in South Africans. METHODS: In this observational study, 1048 adults (median age = 27 y; n = 767 females; n = 473 students) responded to an online survey on work, exercise, screen, alcohol, caffeine and sleep behaviors, depression, anxiety, and insomnia before and during lockdown. Comparisons were made between males and females, and students and nonstudents. RESULTS: During lockdown, males reported larger reductions in higher intensity exercise and alcohol use than females, while depressive symptoms increased more among females, more of whom also reported poorer sleep quality. Students demonstrated larger delays in work and sleep timing, greater increases in sitting, screen, sleep duration, napping, depression and insomnia and larger decreases in work hours, exercise time, and sleep regularity compared with nonstudents. CONCLUSIONS: Students experienced more changes in their routine-oriented behaviors than nonstudents, coupled with larger increases in depression and insomnia. The dramatic change in their work and sleep timing suggests habitual routines that are at odds with their chronotype, with their sleep changes during lockdown likely reflecting "catch-up" sleep in response to accumulated sleep debt under usual routines.