Background: Psychoanalytical theories coincide in understanding depersonalization (DP) as a disorder of narcissistic self-regulation. DP is described as an ego defense against overwhelming shame resulting in a splitting of an observing ego detached from the experiencing self. In contrast to a behavioral-cognitive theory on DP, which suggests that the catastrophic appraisal of normal transient DP maintains the disorder, psychodynamic approaches stress that DP is an important defensive function for the individual. We examine this psychodynamic aspect more closely as it relates to narcissistic self-regulation and interpersonal behavior in depersonalized patients. Sampling and Methods: Thirty-five patients with pathological DP are compared with 28 patient controls concerning their narcissistic self-regulation and interpersonal behavior. For the assessment, we used the German Narcissism Inventory and the Inventory of Interpersonal Problems. The two groups were controlled for sociodemographic data, comorbidity with a personality disorder, and the General Severity Index of the Symptom Check List-90-R. Results: Bonferroni-corrected group comparison showed that the depersonalized patients are characterized by perceiving themselves as helpless, hopeless, socially isolated and worthless, perceiving others as bad and disappointing, and that they avoid interpersonal relations and reality significantly more than other patients with equal symptom severity. Conclusions: Treatment approaches on DP should take the issue of low self-esteem, pervasive shame and the related defensive social avoidance into account. Further empirical research on psychodynamic concepts of DP is warranted also for the sake of linking modern neurobiological findings with clinical experience.