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Burnout is a serious health problem resulting from adverse reaction to prolonged stress in workplaces. The study investigated gender-based significant effects of rational-emotive health education programme on burnout among caregivers of children with developmental disabilities in Enugu State. The study adopted a quasi-experimental research design on a population of 602 caregivers of children with developmental disabilities in 31 registered special needs nursery and primary schools in Enugu State. A total of 120 participants were studied. The Maslach Burnout Inventory-Human Services Survey (MBI-HS) with reliability index of MBI-HSS=0.85 was used for data collection. Mean, standard deviation and ANCOVA were used for all the statistical analysis. The study found that caregivers exposed to REHEP had a reduced mean burnout score in post-intervention than those in the control group. Also, both male and female caregivers had reduced burnout level in the experimental group when compared with their counterparts in the control group. Statistically, significant difference existed on the mean burnout scores of male and female caregivers exposed to REHEP. Statistically, significant difference existed between the mean male and female burnout scores of caregivers who were exposed to REHEP and those not exposed. Since REHEP is significantly effective in reducing and managing burnout among caregivers particularly in the educational sector, other employers of labour should adopt the programme as a reliable psychosocial tool in reducing the burnout levels of their employees for improved productivity, job performance and quality of service delivery in the workplace.