Introduction During the COVID-19 pandemic, many health care workers were involved and suffered significant physical and psychological strain, and nursing was one of the main players. Clearly and objectively establishing the psychological impact on nurses during the pandemic is necessary for long-term recovery and to be prepared for new outbreaks in the future. Aim The aims of this study were to evaluate the perceived impact on nurses at risk of psychological stress at work during a major health care crisis and determine the psychological impact and its influencing factors. Methods An online questionnaire was designed and distributed between April 9 and April 19, 2020, in Spain. The comprehensive self-conducted questionnaire included demographic information and the Psychological Stress and Adaptation at work Score. For the analysis, descriptive statistics, logistic regressions, and receiver operating characteristic curves were determined. Results A total of 825 nurses (33% working in intensive care units and emergency departments) answered the questionnaire. A logistic regression analysis revealed that nurses with higher psychological stress scores experienced more physical overload (P = .02), higher psychological overload (P < .01), poor teamwork (P = .02), more distress due to new circumstances (P < .01), more personal impact of how society responded to COVID-19 (P < .01), anticipation of negative future consequences (P < .01), and worse balance between family and work (P < .01). The area under the curve for the cutoff point of Psychological Stress and Adaptation at work Score 40 was 0.82 (95% confidence interval, 0.79-0.91), with 70% sensitivity and 81% specificity. The positive predictive value was 72%, and the negative predictive value was 80%. Conclusion Psychological Stress and Adaptation at work Score is a rapid and accurate test for evaluating the psychological well-being of health care staff that can be used when crisis prevents the use of conventional stress diagnosis methods. Higher psychological impact was observed in nurses who worked in the intensive care unit and in the hospital ward.