AbstractCerebral palsy (CP) is a major cause of physical disability in childhood. Caregivers are often subjected to both stress and burden due to prolonged care. This article assesses levels, correlates, and predictive factors of stress and caregiver burden among primary caregivers of children with CP. A hospital-based descriptive cross-sectional study was conducted in three tertiary hospitals within the Osun State, Nigeria. Two hundred and nine caregivers were interviewed with both the Parental Stress Scale and Caregiver Difficulty Scale to assess for stress and burden of caregivers, respectively. Data were collected and analyzed using Statistical Program for Social Sciences for Windows version 22 (SPSS Inc., Chicago, Illinois, United States) with alpha set at p < 0.05. Two hundred and nine children with CP aged 12 months to 12 years were seen during the 6-month period. Mothers constituted 87.1% of the total caregivers. The mean (standard deviation [SD]) stress seen in caregivers was 44.8 ± 10.1, while the mean (SD) caregiver burden was 45.2 ± 13.4. Both these scores were above the minimum score of 42, which signifies high psychosocial stress and burden. Multivariate linear regression was used to assess associations between clinical and sociodemographic and each of stress and caregivers' burden. Severity of CP and level of education were the most important predictors of stress, while severity of CP, level of education, and male child were the most important predictors of caregivers' burden. Caregivers' burden and stress are known to result in negative outcomes. Identifying factors that can predict caregivers' burden and stress could help develop an early intervention strategy to minimize these negative effects while promoting caregivers' psychosocial well-being.