Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has driven a global pandemic. Infection control on COVID-19 raises various difficulties faced by healthcare workers in hospitals. The function Infection prevention and control (IPC) is an evidenced-based practical approach to preventing harmful infections in patients and healthcare workers. This study aimed to determine the levels of Knowledge, Management, and Difficulties of Healthcare Workers in the Covid-19 Response in a district hospital in Northern Negros, during the fourth quarter of the Calendar year, 2022. Results shows “very high level” in the level of knowledge, management, and difficulties of healthcare workers in the covid-19 response in the areas of infection control and environment and waste control. And, in the level of difficulties encountered of healthcare workers towards covid-19 response, results shows “high level”. Also, results shows that there is a significant difference in the level of knowledge of health care workers towards Covid 19 response in the area of infection control, environment and waste control, when grouped and compared as to sex. However, when grouped as to age and length of service, there is no significant difference found in the level of knowledge of health care workers towards Covid 19 response. Lastly, there is a significant relationship between the level of knowledge and the level of management of health care workers towards covid-19 response. With the given results, this papers call for the healthcare workers and administrators to continuously support the adaptation of the repeated revisions of the newly created protocol in the management of the dreadful virus, provide an appropriate and comfortable PPE, and enough number of staff must be increased to support in the workplace for the HCW to function properly. Keywords: Knowledge, management, difficulties of healthcare workers, Covid-19, infection control, environment and waste control