SummaryBackgroundMental illness and obesity are among the biggest challenges to population health, they are linked, and may be modifiable during adolescence. We aimed to determine intervening pathways between mental health and BMI z-score symptoms across adolescence.MethodsIn this longitudinal cohort study, we used path models to examine self-reported dieting, happiness with appearance, self-esteem and bullying at 14 years as potential mediators of the cross-lagged relationship between mental health (via the Strengths and Difficulties Questionnaire) and Body Mass Index (BMI) z-score at 11 and 17 years by sex in the UK Millennium Cohort Study, a prospective cohort study of 18,818 children born in the UK between September 1st, 2000, and January 31st, 2002. Full, incomplete data on all singleton children still participating in the study by age 11 years were analysed in GSEM via maximum likelihood estimation (N = 12,450).FindingsWe found happiness with appearance and self-esteem, but not dieting or bullying, mediated the relationship between BMI age 11 and mental health age 17. Each increase in BMI z-score at 11 years was associated with 0.12 increase for boys and a 0.19 increase for girls in scores of unhappiness with appearance (boys:b0.12, 95% C.I.; girlsb0.19, C.I. 0.14 to 0.23) and a 16% increase for boys and a 22% increase for girls in odds of low self-esteem (boys OR 1.16, 95% C.I. 1.07 to 1.26; girls: OR 1.22, 95% C.I. 1.15 to 1.30) at 14 years. In turn, for both boys and girls, being unhappy with appearance and low self-esteem at 14 years were associated with a greater likelihood of emotional and externalizing symptoms at 17 years.InterpretationEarly prevention strategies to encourage healthy physical and mental development of children need to focus on the promotion of positive body-mage and self-esteem.FundingThe10.13039/501100000272National Institute for Health and Care Research(10.13039/501100000272NIHR)10.13039/501100012349School for Public Health Research(10.13039/501100012349SPHR).