We integrate Buddhist thought and psychological science to propose a novel conceptual and operational definition of equanimity. First, we introduce the Decoupling Model of Equanimity—conceptualizing equanimity as the decoupling of desire (wanting and not wanting) from the hedonic tone of current or anticipated experience (pleasant and unpleasant). Second, we propose that equanimity is manifested by an intentional attitude of acceptance toward experience regardless of its hedonic tone, as well as by reduced automatic reactivity to the hedonic tone of experience. Third, we theorize that the practice of mindfulness leads to the cultivation of equanimity. We tested these ideas, focusing on the measurement of equanimity toward unpleasant hedonic tone using self-report scales. Meditation novices (M(SD) age = 31.4(10.9), 65.1 % women), from the general community in Israel, were randomized to a four-session mindfulness training condition (N = 138) or non-intervention control condition (N = 53). Confirmatory factor analyses yielded that, as theorized, equanimity entails one higher-order factor reflecting equanimity, and two lower-order factors—attitude of acceptance and reactivity to unpleasant hedonic tone. Moreover, partially consistent with predictions, we found that relative to the control condition, mindfulness training led to reductions in reactivity to unpleasant hedonic tone over time, as a function of responding to the training (i.e., elevation in state mindfulness). However, training did not lead to expected elevations in attitude of acceptance, regardless of degree of responding to the training. We discuss the implications of these findings for equanimity and mindfulness mechanisms research.