Self-defining memories (SDM) are autobiographical memories associated with the construction and maintenance of identity, and which play a core role in establishing and achieving goals in life. The aim of this study was to evaluate the effort required in retrieving SDM as reflected by physiological activity. We examined the neurovegetative responses associated with three dimensions of SDM: specificity, integrative meaning and emotional valence. Electrodermal activity (skin conductance response frequency, phasic driver) and the high frequency component of heart rate variability (HF-HRV) were recorded during the retrieval of SDM in 36 healthy participants to assess the activation of the sympathetic and parasympathetic systems, respectively. SDM were characterized by three independent investigators with satisfactory inter-rater reliability. Linear mixed effects analyses showed that only the integrative meaning dimension led to a main effect on electrodermal activity. In addition, an interaction effect showed that the retrieval of non-integrative and specific memories was associated with a higher level of electrodermal activity than the retrieval of integrative specific memories. No effects were obtained regarding the HRV indicators. The higher activation of the sympathetic nervous system associated with the retrieval of non-integrative SDM suggests that the ability to derive meaning from personal experiences plays a regulatory role and is a fundamental component in personal adjustment.