Available evidence highlights the importance of emotion regulation in psychological well-being. However, translation of the beneficial effects of ER from laboratory to real-life remains scarce. Here, we present proof-of-principle evidence from a novel cognitive-emotional training intervention targeting the development of ER skills aimed at increasing resilience against emotional distress. This pilot intervention involved training military veterans over 5–8 weeks in applying two effective ER strategies [Focused Attention and Cognitive Reappraisal ] to scenarios presenting emotional conflicts. Training was preceded and followed (...) by neuropsychological, personality, and clinical assessments, and resting-state functional MRI data were also collected from a subsample of the participants. Results show enhanced executive function and psychological well-being following training, reflected in increased working memory, post-traumatic growth, and general self-efficacy. Brain imaging results showed evidence of diminished bottom-up influences from emotional and perceptual brain regions, along with evidence of normalized functional connectivity in the large-scale functional networks following training. The latter was reflected in increased connectivity among cognitive and emotion control regions and across regions of self-referential and control networks. Overall, our results provide proof-of-concept evidence that resilience and well-being can be learned through ER training, and that training-related improvements manifested in both behavioral change and neuroplasticity can translate into real-life benefits. (shrink)