Depression is associated with increased cardiac morbidity and mortality in people with and without cardiac risk factors, and this relationship is, in part, mediated by heart rate variability (HRV). Increased heart rate and reduced HRV are common in depressed patients, which may explain their higher cardiac risk. This pilot study investigated whether mindfulness-based cognitive therapy (MBCT) promoted objective changes in (1) HRV, and (2) depressive symptoms and quality of life, in mental health outpatients. Twenty-seven adults meeting criteria for DSM-IV Axis I disorders completed an 8-week MBCT program. Data were collected on three occasions, 8 weeks apart; twice before and once after MBCT. Participants completed the Short Form-36 and the Center for Epidemiological Studies Depression Scale (CES-D) at each test period. Heart rate and HRV were measured during electrocardiographic monitoring before and after a cognitive stressor. At baseline, 78% of participants met criteria for depression (CES-D ≥16). Multivariate analyses revealed a significant treatment effect for SF-36 physical summary score and depression (as a dichotomous variable), but not for HRV. This pilot study highlights the immediate psychological and health benefits of MBCT. Low power may have influenced the lack of a finding of an association between HRV and MBCT. However, the feasibility of the study design has been established, and supports the need for larger and longer-term studies of the potential physiological benefits of MBCT for cardiac health.