Background: Front-line nurses who provide care for COVID-19 patients have several psychosocial reactions, especially at the beginning of the COVID-19 pandemic. These reactions threaten their health, well-being, and ability to work as well as put them at an increased risk of developing negative coping patterns. The study aimed at exploring front-line nurses' psychosocial reactions and their coping patterns during the COVID-19 pandemic. Study design: Qualitative research was conducted in a sample of 18 nurses who worked at the isolated wards of Al Obour Specialized Hospital, affiliated to Ain Shams University Hospitals. The results of this study revealed that the psychosocial reactions among studied nurses were described into 10 themes as follows: Fear of being infected, feeling uncertainty about the virus, anxiety related to lack of preparation, the feeling of inequality, the feeling of hopelessness and helplessness, concerns about the family, societal stigma, and rejection, feeling of loss and grief, loneliness and social isolation, and physical exhaustion. The study also revealed that although the studied nurses had psychosocial suffering, they have 5 ways of positive coping as follows:  in-service education and training, communicating with family and friends, practicing recreation activities, writing diaries, and practicing spirituality and religious activities. Conclusion: Although frontline nurses suffered from several psychosocial problems during the COVID-19 pandemic, they have positive abilities to cope with their negative emotional stress. Recommendation: Providing support and psychological counseling programs for frontline nurses, especially in times of crisis, should be a part of hospital policy.