Background: Caregivers play an exceptionally important role in the lives of those they provide care for as well as to the healthcare system. The burden of caring for children with mental illness (CWMI) often falls on their caregivers, especially the mothers. Caregivers of CWMI experience significant challenges and are at an increased risk of experiencing mental distress than the general population. Resilience, emotion regulation, and social support are identified as protective factors against mental distress among caregivers. Objective: To determine the prevalence and factors associated with mental distress among caregivers of CWMI attending the child and adolescent mental health clinic at Muhimbili National Hospital (MNH) in Tanzania. Methodology: Hospital-based descriptive cross-sectional study was conducted at MNH Dar es Salaam, Tanzania. A purposive and convenient sample of 120 caregivers of CWMI attending the child and adolescent mental health clinic at MNH were recruited in the study. Interviewer-administered paperless questionnaire consisting of a socio-demographic questionnaire, self-reporting questionnaire (SRQ), 10-item Connor- Davidson Resilience Scale (CD-RISC), Emotion Regulation Questionnaire (ERQ), and Multidimensional Scale of Perceived Social Support (MSPSS) were used to collect data. Data were analyzed using SPSS version 28.0.1.1, where descriptive, bivariate and multivariate analyses were conducted. Results: Among the 120 caregivers studied, 97 (80.8%) were female, and 43 (35.8%) were aged between 35 – 44 years. Among the 120 participants 27 (22.5%) had mental distress, 35 (29.2%) had low resilience, 22 (81.7%) had low cognitive reappraisal, 27 (47.5%) had high expressive suppression, and 5% (6) had low perceived social support. All variables with a p-value of < 0.20 in the bivariate analysis were entered into the multivariate analysis model, where the independent risk of mental distress was four times higher amongst those living out of ..........