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Abstract Study ObjectivesTo investigate associations between social jet lag and the developing adolescent brain. MethodsN = 3507 youth (median (IQR) age = 12.0 (1.1) years; 50.9% females) from the Adolescent Brain Cognitive Development cohort were studied. Social jet lag (adjusted for sleep debt [SJLSC] vs. nonadjusted [SJL]), topological properties and intrinsic dynamics of resting-state networks, and morphometric brain characteristics were analyzed. ResultsOver 35% of participants had SJLSC ≥ 2.0 h. Boys, Hispanic and Black non-Hispanic youth, and/or those at later pubertal stages had longer SJLSC (β = 0.06–0.68, CI = [0.02, 0.83], p ≤ .02), which was also associated with higher Body Mass Index (BMI) (β = 0.13, CI = [0.08, 0.18], p < .01). SJLSC and SJL were associated with lower strength of thalamic connections (β = −0.22, CI = [−0.39, −0.05], p = .03). Longer SJLSC was also associated with lower topological resilience and lower connectivity of the salience network (β = −0.04, CI = [−0.08, −0.01], p = .04), and lower thickness and/or volume of structures overlapping with this and other networks supporting emotional and reward processing and social function (β =−0.08 to −0.05, CI = [−0.12, −0.01], p < .05). Longer SJL was associated with lower connectivity and efficiency of the dorsal attention network (β = −0.05, CI = [−0.10, −0.01], p < .05). Finally, SJLSC and SJL were associated with alterations in spontaneously coordinated brain activity and lower information transfer between regions supporting sensorimotor integration, social function, and emotion regulation (β = −0.07 to −0.05, CI = [−0.12, −0.01], p < .04). ConclusionsMisaligned sleep is associated with widespread alterations in adolescent brain structures, circuit organization, and dynamics of regions that play critical roles in cognitive (including social) function, and emotion and reward regulation.