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Psychophysiological stress markers across concussion recovery milestones have not been examined in an integrated study.To examine physiological (heart rate variability [HRV] and salivary cortisol) and psychological (mood, perceived stress, symptoms, and sleep quality) factors of stress in concussed athletes across clinical recovery milestones.A prospective case control repeated measures study was conducted over three clinical recovery milestones: Symptomatic (acute), Asymptomatic, and 1-week Post Return-to-Play (RTP).Single university athlete program monitored by the university’s sport medicine clinic, Ontario, Canada.Male and female varsity athletes (n=26; M=16, F=10) with medically diagnosed concussion and their matched controls (n=26; M=16, F=10).Physiological: HRV and salivary cortisol; psychological: mood, perceived stress, sleep quality and symptoms.Univariate analyses identified a group by sex interaction for specific HRV measures (RR intervals p=0.0084, Low frequency Power p=0.0084, Mean Heart Rate p=.0049, and Low/High Frequency Ratio p=0.0084). Multivariate analyses of HRV identified main effects for sex and group, and a significant interaction with reduced HF HRV for female concussed athletes through to 1-week post RTP (FDR=.05). HRV suppression was related to mood disturbance in males (FDR.05). Psychological measures were significantly worse for concussed athletes relative to controls at the Symptomatic Phase, but significantly better at 1-week post RTP (paired Wilcoxon at FDR=.05).This study was supported by a grant from the Canadian Institute of Health Research (CIHR) −2012-ABI-CAT1-971 to L. Mainwaring.For both males and females, mood disturbance, symptoms, and sleep quality perturbations were resolved by 1-week post RTP whereas autonomic nervous system disruption persisted beyond RTP in females. Psychophysiological non-invasive markers show promise for concussion monitoring.None.