Job-related burnout is one health outcome in nurses working in neonatal intensive care units (NICUs) due to the heavy workload, which results in negative physical and psychological consequences. One newly introduced approach to improve coping is loving-kindness meditation (LKM). Some studies have shown the effectiveness of the LKM on the mental health of nurses, though more evidence is required to support them. This study aimed to investigate the effectiveness of the LKM on job-related burnout of nurses working in NICU. This clustered controlled randomized clinical trial assessed job-related burnout before and after a month of practicing LKM guided through a virtual method. A total of 66 eligible NICU nurses from 2 referral children hospitals in Tehran were randomly assigned to 2 control (n = 33) and intervention (n = 33) groups. The intervention was performed 3 times a week for 1 month in the form of 20-minute audio files of LKM for the intervention group, and educational files on mental health during the COVID-19 pandemic were sent to the control group. The instruments used in this study were the demographic information questionnaire and the Maslach Burnout Inventory, which participants completed before and after the intervention. The mean difference in the overall scores of burnout before and after the intervention in the intervention group was significantly reduced (P = .003), but no significant difference was observed in the control group (P = .018). These findings support the benefit of LKM in NICU nurses in reducing burnout.