This prospective, longitudinal study examined the influence of baseline physical and psychological burden on serial assessments of health-related quality of life among adults with major burns from three regional burn centers (n = 162). Physical burden groups were defined by % TBSA burned: <10%, 10% to 30%, or >30%. Psychological burden groups were defined by in-hospital distress using the Brief Symptom Inventory Global Severity Index T-score with scores of < 63 or > or = 63. Analyses compared groups across level of burden and with published normative data. Assessments reflected health and function (Short Form 36) during the month before burn, at discharge, and at 6 and 12 months after burn. Physical functioning was significantly more impaired and the rate of physical recovery slower among those with either large physical burden or large psychological burden. Notably, psychosocial functioning also was more impaired and the rate of psychosocial recovery slower among those with greater psychological burden. These results suggest that, in addition to aggressive wound closure, interventions that reduce in-hospital distress may accelerate both physical and psychosocial recovery.