For many people, providing care for a seriously ill family member is a major life event that may disrupt their life and personal goals. Research has demonstrated the experience of such events is often associated with increased symptoms of depression, stress, and anxiety. Although many researchers have examined factors that influence this relation, few have explored it from a motivational perspective. Therefore, the goal of the present study was to examine the influence of self-regulatory processes and motivational orientation on the relations between burden (caregiver and objective burden) and psychological distress (defined as the experience of symptoms of depression, anxiety, and stress). Caregivers of adult family members diagnosed with cancer in the past three years were asked to complete a battery of questionnaires on psychological distress, caregiver burden, objective burden, goal adjustment and regulatory focus orientation. It was predicted that caregiver burden would partially mediate the relation between objective burden and caregiver psychological distress. Furthermore, based on the notion of regulatory fit, the strength of the relation between objective burden and caregiver burden would be greater for caregivers who tend to exhibit a weaker prevention focus than a stronger prevention focus. Lastly, it was hypothesized that the strength of the relation between caregiver burden and psychological distress would be greater for caregivers who report a greater inability to disengage from goals than caregivers who report a greater ability to disengage from goals. Results suggested that objective burden is associated with psychological distress through caregiver burden. Inconsistent with our hypotheses, promotion focus, instead of prevention focus, moderated the relation between objective burden and caregiver burden. Lastly, findings suggest that an ability to disengage from goals alleviates symptoms of anxiety and stress, and an ability to disengage from goals alleviates symptoms of anxiety and stress, and an ability to reengage in goals alleviates symptoms of depressed mood