Informal caregivers are at risk of being overwhelmed by various sources of suffering while caring for their significant others. It is, therefore, important for caregivers to take care of themselves. In the self-care context, mindfulness has the potential to reduce caregiver suffering. We studied the effect of a single session of 20-minute mindful breathing on the perceived level of suffering, together with the changes in bispectral index score (BIS) among palliative care informal caregivers. This was a randomized controlled study conducted at the University of Malaya Medical Centre, Malaysia. Forty adult palliative care informal caregivers were recruited and randomly assigned to either 20-minute mindful breathing or 20-minute supportive listening. The changes in perceived suffering and BIS were measured preintervention and postintervention. The reduction in suffering score in the intervention group was significantly more than the control group at minute 20 (U = 124.0, n1 = n2 = 20, mean rank1 = 24.30, mean rank2 = 16.70, z = −2.095, P =.036). The reduction in BIS in the intervention group was also significantly greater than the control group at minute 20 (U = 19.5, n1 = n2 = 20, mean rank1 = 29.52, mean rank2 = 11.48, z = −4.900, P <.0001). Twenty minutes of mindful breathing was more efficacious than 20 minutes of supportive listening in the reduction in suffering among palliative care informal caregivers.