Background: Carbon monoxide poisoning is a severe health issue worldwide and it is one of the poisonings that results in death in Egypt. So, it is crucial that the public is made aware of it. Objectives: The goal of this study was to evaluate knowledge level, attitude, and preventive practices toward carbon monoxide poisoning in a sample of populations in Sohag governorate, Egypt. Methodology: This cross-sectional study included 600 participants from Sohag governorate's populations. An Arabic-language interviewing survey was used. The questionnaire was consisted of three sections: knowledge, attitude, and preventive practices regarding carbon monoxide poisoning. Results: Evaluating the knowledge level of the participants toward carbon monoxide poisoning showed that 34.7%, 32.8%, and 32.5% of them have poor, moderate, and good knowledge levels respectively. The majority of participants (87.2%) exhibited a positive attitude, while 8.5% had a neutral attitude, and only 4.3% displayed a good attitude. Considering the prevention practices, among the participants, 43.7% shown good behaviors, while 30% exhibited poor practices, and 26.3% displayed moderate activities. Conclusion: Participants' knowledge about carbon monoxide poisoning was limited, but their positive attitude and prevention practices were encouraging. Recommendations: Public health education campaigns and increased awareness on social media and television are recommended.