Abstract Background Women have been assuming more responsibilities and higher positions in major companies, which exposes them to high levels of stress. Higher perceived work stress is related to higher emotional reactivity. Difficulties with emotional regulation can lead to anxiety and mood disorders, which are more prevalent in women than men. Indeed, women leaders are more likely to experience emotional fatigue than men due to excessive empathy. Our aim was to evaluate the associations between self-compassion (SC) scores to depression symptoms, perceived stress and mindfulness, as well as with brain responses to high-arousal unpleasant and pleasant pictures from the International Affective Picture System (IAPS), as measured through functional Magnetic Resonance Imaging (fMRI) in women managers. Methods Forty-six participants were selected for the study. All participants filled the Self Compassion Scale (SCS), Beck Depression Inventory (BDI), Mindful Awareness Attention Scale (MAAS) and the Perceived Stress Scale (PSS). After that they were scanned during an fMRI affective response paradigm. Correlation analysis were performed among these variables. Results Our data suggest that women with higher SC scores respond to affective stimuli with higher activation of the precuneus (a brain region related to self-referential processing), lower levels of stress and depression and show greater attention in everyday activities. Conclusion SC may be an important characteristic for women leaders because of its association with higher sensitivity to emotional stimuli and mindfulness. These skills may allow them to be more aware of others while being less susceptible for stress and depression symptoms.