Background and Objective: Health care workers (HCWs) are at the highest risk of contracting COVID-19, so their knowledge about the disease and their preventive attitude and practice toward COVID-19 are of concern. The present study aimed to assess the knowledge, attitudes, and practices of HCWs toward COVID-19 in Al-Thawra Hospital, Ibb Governorate, Yemen. Materials and Methods: We conducted a cross-sectional survey among HCWs in Al-Thawra Hospital, Ibb, Yemen, from January 1 to March 31, 2022. Results: Of the 80 participants, 50 (62.5%) were males and 30 (37.5%) were females with a mean age of 29.33±7.86 years. About 51.2% of respondents were aware that sneezing is a recognized symptom of COVID-19, while most were unaware of the extrarespiratory symptoms of the disease, such as diarrhea and confusion. About 28.7% of respondents believed that eating or contacting wild animals would result in infection by the COVID-19 virus, with the majority (71.3%) agreeing that wearing a well-fitting face mask effectively prevents COVID-19 infection. Approximately 48 respondents (60.0%) believed that washing hands could prevent contracting COVID-19, and only 31 (38.7%) agreed that if a patient shows signs and symptoms of COVID-19, they can confidently participate in that patient’s treatment. In response to avoid COVID-19, about 23 respondents (28.7%) had always gone to crowded places, and 35 (43.6%) had always worn face masks at every contact with patients, while only 14 (17.5%) of participants refrained from shaking hands and 37 (46.3%) always washed their hands before and after handling each patient. Conclusion: This study showed that most respondents have poor knowledge regarding the clinical picture of COVID-19 and its mode of transmission as most of them failed to detect an extrapulmonary manifestation of COVID-19 and were unaware of the possibility of transmission of the disease from wildlife. In addition, the attitude and preventive practice of the respondents were unsatisfactory in containing the transmission of the disease.