It is not surprising that smoking abstinence rates are low given that smoking cessation is associated with increases in negative affect and stress that can persist for months. Mindfulness is one factor that has been broadly linked with enhanced emotional regulation. This study examined baseline associations of self-reported trait mindfulness with psychological stress, negative affect, positive affect, and depression among 158 smokers enrolled in a smoking cessation treatment trial. Several coping dimensions were evaluated as potential mediators of these associations. Results indicated that mindfulness was negatively associated with psychological stress, negative affect, and depression and positively associated with positive affect. Furthermore, the use of relaxation as a coping strategy independently mediated the association of mindfulness with psychological stress, positive affect, and depression. The robust and consistent pattern that emerged suggests that greater mindfulness may facilitate cessation and attenuate vulnerability to relapse among smokers preparing for cessation. Furthermore, relaxation appears to be a key mechanism underlying these associations.