Depression is associated with high levels of mind-wandering and low levels of self-compassion. However, little is known about whether and how these two factors interact with one another to influence depressive symptoms. The current study examined the interaction between mind-wandering, self-compassion, and depressive symptoms in a depressed sample and tested the effects of an 8-week mindfulness-based cognitive therapy (MBCT) program on these constructs. At baseline, mind-wandering was associated with higher depressive symptoms only among individuals with low self-compassion. Self-compassion additionally predicted depressive improvement. As expected, MBCT increased self-compassion and reduced mind-wandering compared with a treatment-as-usual control group. Overall, longitudinal changes in self-compassion produced a moderation effect similar to the one at baseline so that increases in mind-wandering were associated with increases in depressive symptoms only among those who decreased in self-compassion. Results provide the first evidence that self-compassion can protect against the deleterious effects of mind-wandering among depressed participants, both at baseline and longitudinally. Findings also suggest that self-compassion is an effective predictor of depressive improvement. Finally, MBCT is effective not only at reducing depressive symptoms, but also at targeting protective and risk factors associated with depression. (PsycINFO Database Record (c) 2018 APA, all rights reserved)