The current study evaluated the construct validity and sensitivity to change of the Spectra: Indices of Psychopathology in an inpatient psychiatric sample (N = 83). Admission diagnoses were generally split between Depression / Anxiety (27.7%), Substance Use Disorders (27.7%), Bipolar Disorder (22.9%), and Primary Psychotic Disorders (21.7%). Results indicate the three higher-order spectra scores (Internalizing, Externalizing, and Reality Impairing) effectively differentiated between known clinical groups, with effect sizes (ηp2) ranging from 0.13 (Internalizing) to 0.44 (Externalizing). Hypothesized spectra scores also discriminated between groups with and without a history of suicide attempts (Internalizing Cohen’s d = 0.60), arrests within the last five years (Externalizing Cohen’s d = 0.60), and a primary psychotic disorder diagnosis at admission (Reality Impairing Cohen’s d = 1.12). Concurrent validity was supported when examining patterns of correlations with the Personality Assessment Inventory; all target correlations were statistically significant (p < 0.05) and ranged from r = 0.36 (Psychotic Experience) to r = 0.76 (Depression). Finally, sensitivity to change assumptions were met when comparing admission and discharge scores for the subsample (N = 47) of patients who also completed the instrument at discharge. The implications with respect to application and clinical utility in acute (inpatient) settings are discussed.