The aims of the present study were to explore three dimensions of the Maslach Burnout Inventory (MBI) in a sample of mothers; to compare the burnout levels, stress symptoms, coping styles and perceived social support of mothers with mentally handicapped and healthy children; lastly, to investigate the predictive level of the stress symptoms, coping styles and perceived social support on the burnout levels of the two group of mothers. The sample consisted of 118 mothers of mentally handicapped and 121 mothers of healthy children. The validation of MBI in a sample of the mothers of mentally handicapped and healthy children yieled two factors of emotional burnout and personal accomplishment. The results of one way ANOVAs indicated that there were significant differences between the emotional burnout levels and submissive coping style levels of the two group of mothers, the mothers of mentally handicapped children having higher scores than the mothers of the healthy children on two factors of MBI and the submissive coping style factor of the Coping Style Scale. Hierarchical regression analysis revealed that personal accomplishment factor of MBI, cognitive-affective factor of the Stress Self-Assessment Checklist, submissive style factor of the Coping Style Scale and seeking for social support factor of the Multidimensional Scale of Perceived Social Support Scale were the best predictors of burnout in the mothers of the mentally handicapped children. Hierarchical regression analysis also revealed that the family factor of the Multidimensional Scale of Perceived Social Support Scale, cognitive-affective factor of the Stress Self-Assessment Checklist, helpless style factor of the Coping Style Scale, physiological symptom factor of the Stress Self-Assessment Checklist and confidence in self factor of the Coping Style Scale were the best predictors of burnout in the mothers of the healthy children. The results were discussed in the context of the related literature.