Considering direct and indirect evidence of associations between deficits in personality functioning and high somatic morbidity, our exploratory study determined whether and, if so, which physical illnesses may be associated with impairments in personality functioning. A large sample of diagnostically heterogeneous psychotherapy inpatients (N = 5401) was assessed with the short version of the Structural Questionnaire of the Operationalized Psychodynamic Diagnosis (OPD-SQS) and the Work Ability Index (WAI). In addition, discharge diagnoses were recorded. For a subsample (N = 2582), levels of personality functioning were assessed by their therapists according to the OPD system. While consistent associations were found between personality functioning and neurological, urogenital, dermatological, and musculoskeletal disorders, findings on possible associations with other disorders revealed inconsistencies. The number of diseases as surrogate marker for disease burden was significantly associated with several indicators of personality functioning. Our results suggest associations between impairments in personality functioning and poor physical health. We discuss potential mechanisms as well as clinical implications.