ObjectiveTo examine the association of 24-hour time-use compositions with mental health in a large, geographically diverse sample of UK adolescents.DesignCross-sectional, secondary data analysis.SettingMillennium Cohort Study (sixth survey), a UK-based prospective birth cohort.ParticipantsData were available from 4642 adolescents aged 14 years. Analytical samples for weekday and weekend analyses were n=3485 and n=3468, respectively (45% boys, 85% white ethnicity).Primary and secondary outcome measuresPrimary outcome measures were the Strengths and Difficulties Questionnaire (SDQ, socioemotional behaviour), Mood and Feelings Questionnaire (MFQ, depressive symptoms) and Rosenberg Self-Esteem Scale (RSE, self-esteem). Behavioural exposure data were derived from 24-hour time-use diaries.ResultsOn weekdays, participants spent approximately 54% of their time in sleep, 3% in physical activity, 9% in school-related activities, 6% in hobbies, 11% using electronic media and 16% in domestic activities. Predicted differences in SDQ, MFQ and RSE were statistically significant for all models (weekday and weekend) that simulated the addition or removal of 15 min physical activity, with an increase in activity being associated with improved mental health and vice versa. Predicted differences in RSE were also significant for simulated changes in electronic media use; an increase in electronic media use was associated with reduced self-esteem.ConclusionSmall but consistent associations were observed between physical activity, electronic media use and selected markers of mental health. Findings support the delivery of physical activity interventions to promote mental health during adolescence, without the need to specifically target or protect time spent in other activities.