Recent findings have highlighted the adverse consequences of burn injuries, including pain, physical dysfunction, and high levels of psychological distress. While these “outcome variables” are all inter-related, prior studies have used global measures of distress which do not separate anxiety and depression. Determining what aspects of distress are most strongly linked with pain-related outcomes is important, since the preferred treatment approaches for depression and anxiety may differ. We assessed the unique prospective effects of anxiety and depression on pain and functional outcomes in a total of 524 subjects hospitalized for serious burn injuries. Subjects completed measures of quality of life (the SF-36) and psychological distress (Brief Symptom Inventory) at discharge and at 6, 12, and 24 months post-discharge. We conducted linear mixed effects analyses to model anxiety and depression's unique longitudinal effects; BSI depressive and anxiety symptoms at each time point were studied as predictors of subsequent changes in pain, fatigue, and physical function. Moreover, we controlled for demographic variables, pre-burn health status, and characteristics of the burn injury. When included alone in prediction models, both depression and anxiety were strong prospective predictors of pain, fatigue, and physical dysfunction at the subsequent time point (p's< .01). However, when both were included together in order to study their unique effects, depressive symptoms (but not anxiety) emerged as a significant predictor of subsequent increases in pain (Z=2.2, p< .05) and reductions in physical functioning (Z=2.3, P< .05), while anxiety (but not depression) predicted subsequent elevations in fatigue (Z=2.3, P< .05). These findings suggest potentially distinct effects of depression and anxiety as a function of the outcome variable under study, and imply that assessment and treatment of both depressive and anxiety symptoms may help improve a broad range of long-term pain-related outcomes following burn injury.