AbstractObjectives: Cognitive reserve (CR), defined as individual differences in the ability to cope with brain damage, seem to be associated to the several psychopathological features in psychiatric patients, such as the functional outcome. This study aims to identify different profiles of CR by combining intelligence quotient (IQ) and premorbid functioning, two measures independently associated to CR in previous works, as well as to explore CR effect on both Theory of Mind (ToM) baseline performance and improvement after socio-cognitive trainings. Methods: Sixty patients with chronic schizophrenia underwent a socio-cognitive rehabilitation. All patients were assessed for psychopathology, neurocognition, and ToM at baseline and post-treatment. CR profiles were explored with K-means cluster analysis, while differences between clusters in both baseline assessments and post-treatment ToM improvement, were analyzed by means of analysis of variance and repeated measures analysis of covariance. Results: The analysis revealed three CR profiles, respectively, characterized by low early premorbid functioning and mild intellectual impairment, average/high early premorbid functioning trend with moderate intellectual impairment and good early premorbid functioning associated to IQ within normal limits. Analyses showed a significant effect of CR on both baseline ToM performance and treatment outcome: patients with higher CR reached significantly better ToM scores. Conclusions: These results underline the clinical relevance of defining CR profiles of patients to customize trainings: subjects with a lower CR may benefit from more intensive programs. A deeper knowledge about CR may considerably increase our understanding of individual differences and thus potentiate treatment outcome. (JINS, 2018, 24, 563–571)