Altruism, defined as costly other-regarding behavior, varies considerably across people and contexts. One prominent context in which people frequently must decide on how to socially act is under stress. How does stress affect altruistic decision-making and through which neurocognitive mechanisms? To address these questions, we assessed neural activity associated with charitable giving under stress. Human participants (males and females) completed a charitable donation task before and after they underwent either a psychosocial stressor or a control manipulation, while their brain activity was measured using functional magnetic resonance imaging. As the ability to infer other people's mental states (i.e., mentalizing) predicts prosocial giving and may be susceptible to stress, we examined whether stress effects on altruism depend on participants' general capacity to mentalize, as assessed in an independent task. Although our stress manipulation per se had no influence on charitable giving, increases in the stress hormone cortisol were associated with reductions in donations in participants with high mentalizing capacity, but not in low mentalizers. Multivariate neural response patterns in the right dorsolateral prefrontal cortex (DLPFC) were less predictive of postmanipulation donations in high mentalizers with increased cortisol, indicating decreased value coding, and this effect mediated the (moderated) association between cortisol increases and reduced donations. Our findings provide novel insights into the modulation of altruistic decision-making by suggesting an impact of the stress hormone cortisol on mentalizing-related neurocognitive processes, which in turn results in decreased altruism. The DLPFC appears to play a key role in mediating this cortisol-related shift in altruism. SIGNIFICANCE STATEMENT Altruism is a fundamental building block of our society. Emerging evidence indicates a major role of acute stress and stress-related neuromodulators in social behavior and decision-making. How and through which mechanisms stress may impact altruism remains elusive. We observed that the stress hormone cortisol was linked to diminished altruistic behavior. This effect was mediated by reduced value representations in the right dorsolateral prefrontal cortex and critically depended on the individual capacity to infer mental states of others. Our findings provide novel insights into the modulation of human altruism linked to stress-hormone dynamics and into the involved sociocognitive and neural mechanisms, with important implications for future developments of more targeted interventions for stress-related decrements in social behavior and social cognition.