Purpose: We assessed sex-and age-dependent differences in a cross-sectional analysis of cardiac autonomic nervous system (ANS) regulation during sleep in adolescents.Methods: Nocturnal heart rate (HR) and heart rate variability (HRV) metrics, reflecting ANS functioning, were analyzed across the night and within undisturbed rapid eye movement (REM) and non-REM sleep in 149 healthy adolescents (12-22 years; 67 female) from the National Consortium on Alcohol and Neurodevelopment in Adolescence.Results: Nocturnal HR was slower in older, more pubertally advanced boys than in younger boys. In girls, HR did not vary according to age or maturity, although overall HRV and vagal modulation declined with age. Although younger boys and girls had similar HR, the male-female HR difference increased by similar to 2.4 bpm every year (p < .01, higher in older girls). Boys and girls showed expected increases in total HRV across the night but this within-night "recovery" was blunted in girls compared with boys (p < .05). Also, the non-REM and REM difference in HR was greater in girls (p < .01). Models exploring a role of covariates (sleep, mood, reproductive hormones, activity) in influencing HR and HRV showed few significant effects, apart from sedentary activity (higher in older girls), which partially mediated the sex x age interaction in HR.Conclusions: Sex-related differences in cardiac ANS function emerge during adolescence. The extent to which sex-age divergences in ANS function are adaptive or reflect underlying sex-specific vulnerability for the development of psychopathology and other health conditions in adolescence needs to be determined. (C) 2018 Published by Elsevier Inc. on behalf of Society for Adolescent Health and Medicine.