Objective The COVID-19 pandemic resulted in heightened stress for nurses and other healthcare workers, particularly during the initial phase of the crisis. Despite the adoption of various coping strategies, psychological distress persisted, affecting nurses' well-being and jeopardizing the overall resilience of the healthcare system. This study assessed the emotional response, perceived stressors, and coping strategies among nurses' staff who worked during the first wave of COVID-19 pandemic. Method A cross-sectional study was carried out among nurses who worked during the initial phase of the COVID-19 crisis (June - August 2020), at a tertiary care center in Western Saudi Arabia. The questionnaire explored five main sections. The first section (15 items) assessed emotions experienced during the initial wave of COVID-19, capturing both positive and negative sentiments, such as "joy"or "fear." The second section (20 items) examined the presence of stressors, like "lack of protective equipment" or "fear of infection." The third section (14 items) evaluated the perceived effectiveness of certain stress-reducing factors, including "peer support" or "training." In the fourth section (13 items), participants rated their usage frequency of various coping strategies, such as "meditation" or "seeking advice." Lastly, the fifth section assessed the hypothetical impact of 10 incentives, like "financial bonuses" or "additional training," in motivating nurses' involvement in future epidemic responses. The questionnaire was completed with demographic and professional data. A convenience sampling method was employed, and 315 nurses participated in the study. Descriptive statistics were carried out using SPSS version 24 for Windows(IBM Corp., Armonk, NY). Result The most commonly experienced emotion was a feeling of responsibility and ethical duty, reported by 97.5% of the participants, followed by nervousness and fear (83.8%), anger (73.3%), and stigma (70.2%). On the other hand, 86.7% were expecting a financial compensation. The most common stressors were related to the nurses' own safety, or the safety of their families and colleagues, reported by 92.4-95.2% of the participants. The perceived uncontrollability of COVID-19 was also a significant stressor. The improvement of the health status of infected colleagues (98.1%) or patients (97.5%) were the most common factors associated with the reduction in nurses' stress. Among the coping strategies, five were almost systematically deployed by the nurses (>95%), all consisting of cognitive and behavioral mechanisms to enhance own knowledge and safety and avoid being infected. The most crucial determinants for commitment in future pandemics are the availability of a cure or vaccine (93.3%), family support (91.4%), adequate personal protective equipment from the hospital (90.8%), and exemption from overtime (90.2%). Conclusion The first wave of COVID-19 exerted a tremendous psychological stress on nurses, due to concerns about safety, disease uncertainties, and social isolation. Analyzing these impacts offers insights for enhancing institutional and national crisis strategies, emphasizing staff safety and psychological well-being, especially for first responders like nurses. Policy implications include prioritizing mental health support and preparedness in future crisis plans. Additionally, ensuring continuous training and strategic workload management is crucial for maintaining frontline commitment.