Background: The pandemic of coronavirus disease 2019 placed multifaceted challenges for nurse managers’ achievement of their roles’ activities efficiently. Political skills are the essential tool for communicating successfully, influencing nursing staff’s work, and responding to emergency events and obstacles during crises. Aim: This study aimed to determine the effectiveness of nurse managers’ political skills on preparedness and response activities during coronavirus disease 2019 outbreak. Design: It was utilized a comparative, correlational design. Setting: It was conducted at El Mahalla El Kobra General Hospital in Intensive Care Units, operation, isolation, and inpatient wards. Subjects: It involved all nurse managers (51) and 203 nursing staff. Tools: The study’s questionnaire consisted of three parts; involving demographic data, assessment of preparedness and response activities of COVID-19, and political skills inventory. Results: The majority of NMs had high levels of political skills and were satisfied with their activities during the preparedness and response of Covid-19. Furthermore, the nursing staff was satisfied with nurse managers’ activities of communication & information sharing and education, ethical and legal practice, incident management, and intervention, but not with the activities of preparation and planning, safety & security, and psychological support. Conclusion: Nurse Managers need to possess strong political skills to have the social power of attaining their roles’ activities during the COVID-19 crisis. Recommendations: Developing a periodic in-service training program on political skills, as well preparedness, responses, recovery, and evaluation of disasters.