Objective: Promoting smoking cessation through effective health messaging among African American smokers is of great urgency as African Americans suffer disproportionally more from smoking-related diseases compared to White smokers. This research examines the potential impact of self-affirmation on reducing defensive processing of graphic cigarette warning labels among African American smokers. Method: We conducted an experimental study in which participants were instructed to self-affirm (or not) prior to viewing graphic cigarette warning labels. Results: We found that although self-affirmation had no main effect on defensive processing, it interacted with initial/preexisting attitudes towards smoking to influence defensive responses such as message derogation and perceived message manipulation. For participants with more positive initial attitudes towards smoking, self-affirmation led to reduced message derogation and perceived message manipulation. For these individuals, we also found an indirect effect of self-affirmation on intentions to quit smoking through perceived message manipulation. Self-affirmation had largely no effects on participants with less positive initial attitudes towards smoking. Conclusion: The theoretical and practical implications of these findings are discussed.