Background and Aim: Children with special needs such as those with hearing loss, visual impairment, mental retardation, and physical-motor disability have special conditions, which may adversely affect their parents’ mental health. Given the importance of this issue, the pre-sent study aimed to investigate and compare the components of quality of life and psychological well-being in mothers of children with hearing loss, visual impairment, mental retardation, and physical-motor disability.Methods: This was a descriptive, retrospective study. The statistical population included all mothers of children with special needs. The participants of this study were 200 mothers of children with special needs that were divided into four groups of hearing loss, visual impairment, mental retardation, and physical-motor disability in Isfahan. The mothers were selected thro-ugh stratified random sampling. Data were collected using quality of life and psychological well-being questionnaires.Results: In terms of quality of life, there was a statistically significant difference between mothers of children with hearing loss and mot-hers of children with mental retardation and physical-motor disability (p<0.05). However, no significant difference was observed between mothers of children with hearing loss and mot-hers of children with visual impairment. No significant difference was also observed among the four groups of mothers in terms of psycho-logical well-being (p>0.05).Conclusion: Although the quality of life in both groups of mothers of hearing and visually impaired children was higher than that of mothers of children with mental retardation and physical-motor disability, the physical and mental health of these mothers should be taken into consideration.