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Background: Neonatal jaundice is a major reason babies are frequently re-admitted after hospital discharge following delivery. One means of improving neonatal care and reducing potential mortality associated with neonatal jaundice in resource-limited settings is to create awareness among caregivers. Caregivers who tend to have higher knowledge and awareness, also have positive attitudes, and are not guided by outmoded socio-cultural beliefs and practices are more likely to seek early care and treatment for neonatal jaundice., Objective: This study investigated caregivers' knowledge, attitude and practices regarding neonatal jaundice in a tertiary health facility in the Volta region of Ghana., Methods: This was a descriptive cross-sectional study that employed a quantitative approach for data collection. A total of 202 caregivers from the Ho Teaching Hospital in the Volta region of Ghana were sampled using a systematic random sampling strategy where quantitative data was collected using a questionnaire and analyzed with STATA version 14.0. Ordered logistic regression was used to determine the factors that were associated with caregivers' knowledge regarding neonatal jaundice and attitude after controlling for relevant covariates., Results: Less than half of the caregivers demonstrated good knowledge (45.5%) and attitude (47.5%) but 58.9% had good practices regarding neonatal jaundice. Caregivers who had prior awareness and education on neonatal jaundice were three times more likely to have good knowledge about jaundice than those without previous education [AOR = 3.02, (95%CI: 1.59-5.74), p = 0.001]. A caregiver employed in the public sector was two times more likely to have a good attitude about jaundice than those employed in the private sector [AOR = 2.08, (95%CI: 1.03-4.21), p = 0.042]., Conclusion: Less than two thirds of the caregivers demonstrated good practice with limited knowledge and poor attitude. Efforts to promote well informed and improved caregivers' attitude will advance positive maternal health-seeking behavior and reduce disabilities and death through early detection and intervention of infants with neonatal jaundice. Public awareness and education about neonatal jaundice especially among caregivers in the private sector should also be intensified., Competing Interests: The authors have declared that no competing interests exist.