Extensive research demonstrates that exposure to threatening anti-tobacco messages can lead to defensive message processing which reduces message effectiveness. However, research investigating whether this effect is moderated by the smoking status of the message viewer is lacking. In this study, participants (N = 48 smokers and N = 51 non-smokers) viewed and rated secondhand smoke anti-tobacco messages depicting both smoking cues and threat content, or messages depicting neither while heart rate, skin conductance, and facial EMG were recorded. Post viewing, self-reported emotional experience, level of counterarguing, and recognition memory were measured. In support of the LC4MP, there were no differences between smokers and non-smokers’ responses for non-threatening messages absent in smoking cues. However, messages that contained both smoking cues and threat content were defensively processed by smokers–but not non-smokers–as indicated by significantly faster heart rate, lower recognition memory and higher self-reported negativity, arousal, and counterarguments. The theoretical and practical implications are discussed.