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Background: Since the occurrence of the COVID-19 pandemic, different public health measures have been implemented to prevent and control the further spread of the disease. However, barriers that influence the effective implementation of public health measures were not explore in Ethiopia especially in study Area. Therefore, this study tried to fill this gap by exploring the barriers to effective implementation of public health measures for prevention and control of the COVID-19 pandemic in the Gamo Zone of southern Ethiopia. Methods: The study employed a qualitative study with a phenomenology approach among purposely selected 30 individuals in the community and selected institutions. Key informant interview was used to collect the data. The data were transcribed verbatim and translated into the English language. The transcribed data were read several times to clearly understand the content for further analysis. The analysis of the data was conducted based on the modified Tanahashi framework. Results: The study identified different barriers under five main themes: accessibility, acceptability, availability, contact and use, and effective implementation of public health measures related to barriers. The main barriers to effective implementation of public health measures were resistance to change, negligence, lack of community engagement, insufficient training for front line workers, poor supportive supervision, poor law enforcement, and lack of continuous community awareness creation. Beside, acceptability related barriers like cultural and religious norms and availability related barriers like shortage of personal protective equipment and shortage of skilled health professional have also lion share barriers for implementation of the public health measures. Conclusion: The study identified different personal, institutional, and societal level barriers for effective implementation of public health measures for the COVID-19 pandemic. Therefore, proper and targeted continuous community awareness creation with further mandatory law enforcement activities should be implemented by the concerned bodies to mitigate individual and societal level barriers. In addition, the government with relevant stakeholders should give due attention to equip and protect the frontline professionals by availing the necessary logistic and provision of continuous capacity-building activities. [ABSTRACT FROM AUTHOR]