["Journal of Child Psychology and Psychiatry, EarlyView. ", "\n\nBackground\nLoneliness in childhood is a growing public health concern, yet early multilevel candidate risk and protective factors remain insufficiently mapped. Systematic investigation is essential to guide prevention and intervention during sensitive developmental periods. This study identifies environmental, health, and neurobiological factors associated with prospective loneliness in children.\n\n\nMethods\nA population‐based longitudinal cohort study used data from children aged 9–10 years and their caregivers enrolled in the Adolescent Brain Cognitive Development (ABCD) Study between 2016 and 2022. A total of 9,602 children with complete baseline and follow‐up loneliness and demographic data were included after exclusions for exposure completeness and quality assurance. Baseline measures included 347 environmental exposures, 61 health indicators, and 558 MRI features capturing gray matter volume, white matter microstructure, and resting‐state functional connectivity. The primary outcome was prospective loneliness reported from ages 10–14. Linear mixed‐effects models assessed associations with environmental and health variables. Linear discriminant analysis was applied to neuroimaging features to distinguish children with and without prospective loneliness.\n\n\nResults\nAmong 9,602 children (mean [SD] age, 119.01 [7.52] months; 48% girls; 55% White, 14% Black, 31% other races/ethnicities), 12% (n = 1,158) reported loneliness at baseline, and 71.6% (n = 829) of those re‐experienced loneliness over 3 years. Prospective loneliness was significantly associated with 40 environmental variables (|d| = 0.069–0.388), most strongly parental psychopathology, developmental history, and family income. Twenty‐six health indicators were also associated (|d| = 0.061–0.390), with general mental health showing the largest effect. Neuroimaging features associated with prospective loneliness converged in brain systems involved in socioemotional processing.\n\n\nConclusions\nProspective loneliness was associated with modifiable environmental and health factors, as well as neurobiological differences. Early identification and targeted interventions that support socioemotional development, particularly within family, neighborhood, and school contexts, may help mitigate loneliness and its long‐term impact.\n\n"]