Poor wellbeing and burnout are significant issues among health-care professionals (HCPs) and may contribute to unsafe practice. In this exploratory study, we aimed to: provide the first investigation of the combined and unique influences of these psychological factors in predicting safe practice; confirm the role played by mindfulness in relation to wellbeing, burnout and safe practice; and investigate whether values and self-compassion predict additional variability above and beyond mindfulness skills. Ninety-eight NHS staff completed measures of wellbeing, burnout, perceived safety of practice, mindfulness, values and self-compassion. Practitioners with higher perceived safety of practice reported higher levels of mindfulness, but not values or self-compassion, particularly lower experiential avoidance and nonjudgmental attitude toward difficult thoughts. Mindfulness explained significant variability in psychological distress (20%), emotional exhaustion (8%), cognitive weariness (10%), patient safety related to oneself (7%), and related to work (8%). Values (obstruction) added unique variance for psychological distress (12%) and physical fatigue (10%). Moreover, self-compassion explained a small yet significant portion of variability in emotional exhaustion. These preliminary findings suggest that mindfulness processes may be associated with perceived safety of practice. The results also indicate that mindfulness-based interventions for HCPs may benefit from the inclusion of values-based action components and self-compassion practices.