The objectives of the research are 1) To assess the relationship in emotional distress, social isolation and psychological well-being among care givers of children with cleft lip and cleft palate. 2) To confirm mediating role of social isolation between emotional distress and wellbeing. This cross-sectional correlational research was conducted in Department of Psychology, University of Gujrat after approval from ASRB and data was collected between January to April, 2021. A sample of 200 caregivers visiting cleft hospital in Gujrat with their children who have cleft lip and cleft palate was purposively selected. There were 96 males and 104 females between age range 20 to 75 years old (M=34.71, SD=10.80). Majority was educated, residing in rural areas of Gujrat in joint family system. Urdu versions of three standardized scales were used for data collection, Caregiver Social Isolation Scale (CSIS, Shafiq & Amwar-ul-Mustafa, 2022), Psychological Wellbeing Scale (PWS, Boztepe, Çınar, & Özgür, 2020) and Depression, Anxiety, Stress Scale (DASS-21, Lovibond, & Lovibond, 1995) to measure emotional distress. Permissions were taken before using the scales from the test developers and translators. The results showed that there is a significant relationship between emotional distress (Depression, Anxiety and Stress), social isolation and psychological well-being among caregivers of children with cleft lip and cleft palate. Social Isolation has positive significant positive relationship with depression, Anxiety, stress and negative significant relationship with psychological well-being and has mediated either partially or fully among them. Depression has partially strengthened social isolation to mediate with wellbeing of caregivers. However, anxiety and stress has completely enhanced this withdrawal to weaken their sense of wellness. Implications are discussed in the light of the findings. Keywords: Caregivers, Child, Hospitalized, Cleft Lip, Cleft Palate, Congenital Abnormalities, Social Isolation.