Health-risk information can elicit negative emotions like anticipated regret that may positively affect health persuasion. The beneficial impact of such emotions is undermined when target audiences respond defensively to the threatening information. We tested whether self-affirming (reflecting on cherished attributes) before message exposure can be used as strategy to enhance the experience of anticipated regret. Women were self-affirmed or not before exposure to a message promoting fruit and vegetable consumption. Self-affirmation increased anticipated regret and intentions reported following message exposure and consumption in the week after the intervention; regret mediated the affirmation effect on intentions. Moreover, results suggest that anticipated regret and intentions are serial mediators linking self-affirmation and behavior. By demonstrating the mediating role of anticipated regret, we provide insights into how self-affirmation may promote healthy intentions and behavior following health message exposure. Self-affirmation techniques could thus potentially be used to increase the effectiveness of health communication efforts.