Distress intolerance has been studied as a transdiagnostic mechanism implicated in a variety of forms of psychopathology and psychological treatments. Although past research has largely supported the separability of distress intolerance from related constructs, some evidence indicates that it overlaps to a meaningful degree with demoralization and negative emotionality, two affect-laden psychopathology-vulnerability factors. The goal of the current study was to clarify the position of the distress intolerance construct in a nomological network that includes demoralization and negative emotionality. Using a sample of 402 undergraduate students, we performed confirmatory factor analyses to examine the underlying structure of distress intolerance, demoralization, and negative emotionality. We also conducted zero-order correlational and hierarchical regression analyses to examine whether distress intolerance predicts unique variance in theoretically relevant psychological constructs above and beyond demoralization and negative emotionality. Results indicated that, although distress intolerance, demoralization, and negative emotionality demonstrate similar patterns of associations with external criteria, the constructs are structurally distinct and distress intolerance accounts for unique variance in psychological outcomes. Overall, our findings support the construct validity of distress intolerance as empirically separable from both demoralization and negative emotionality. Clinical implications, limitations, and future directions are discussed.