Purpose: To identify the impact of dealing with COVID-19 patients in clinical areas on nurses' professional self-concept and self-confidence. Background: Professional self-concept is considered a critical factor in the recruitment/retention process in nursing, nursing shortage, career satisfaction, and academic achievements. Professional self-confidence is also a crucial determinant in staff satisfaction, reducing turnover, and increasing work engagement. Design: Descriptive, comparative study. Methods: The study was conducted between February to May 2021 by utilizing a convenience sampling technique. A total of 170 nurses from two facilities were recruited from two COVID-19 and non-COVID-19 designated facilities. The level of professional self-concept and self-confidence was assessed by utilizing the Nurses' Self-Concept Instrument and Self-Confidence Scale. Results: The professional self-concept level among the exposed group to COVID-19 patients was lower than the comparison group, while the professional self-confidence level among the exposed group to COVID-19 patients was similar to the comparison group. On the other hand, the satisfied staff and those who received professional training in dealing with COVID-19 patients reported a higher level of professional self-concept. Conclusions: Dealing with COVID-19 patients has an impact on professional self-concept; the exposure group was lower than those who did not deal with COVID-19 patients, while the professional self-confidence level among the exposed group was similar to the comparison group. Getting professional training in dealing with COVID-19 patients and being satisfied at work were significant factors in improving the professional self-concept. Policymakers should create strategies that target the improvement of professional training in dealing with COVID-19 patients.