BACKGROUND: This study examined early life antecedents of childhood social isolation, whether these factors accounted for poor outcomes of isolated children, and how these associations varied according to patterns of stability and change in childhood isolation. METHODS: Participants included 2232 children from the Environmental Risk (E-Risk) Longitudinal Twin Study. We conducted growth mixture modelling (GMM) on combined parent and teacher reports of childrens social isolation when children were 5, 7, 10 and 12 years, and we assessed associations with age-5 antecedents and age-18 outcomes using regression analyses. RESULTS: We identified three linear developmental trajectories of increasing (4.75%), decreasing (5.25%) and low stable (90.00%) social isolation. Age-5 attention deficit hyperactivity disorder (ADHD) symptoms, emotional problems, prosocial behaviours, maternal personality (openness) and size of school were associated with the decreasing trajectory of social isolation. When controlling for these antecedents, increasingly isolated children were still more likely to experience ADHD symptoms, loneliness, lower job optimism and lower physical activity at age 18. CONCLUSIONS: Isolated children follow distinct patterns of change over childhood and isolation seems most detrimental to health at the time it is experienced. Social isolation can be a valuable indicator of co-occurring problems and provide targets for mental health intervention in young people.