Purpose: The purpose of this study was to explore nurses’ experience with caring for COVID-19 patients in a negative pressure room amid the spread of the pandemic. Methods: This study was a qualitative research, and focus group interviews were used to collect data. Three focus groups comprising 19 nurses were interviewed from February 17 to 25, 2021. All interviews were recorded and transcribed verbatim with the consent of the participants. The verbatim transcripts were scrutinized using thematic analysis. Results: Two main themes emerged from the analysis: ‘Struggling in an isolated space’ and ’Limitations of nursing infrastructure and system’. The nurses caring for COVID-19 patients experienced anxiety and fear about the infection, physical exhaustion, emotional burnout, and a sense of duty as a nurse. They also acknowledged the lack of guidelines, increased task and burden, limitations of nursing care, and the demand for improving the limitations of the nursing system. Conclusion: The results of this study demonstrate that nurses caring for COVID-19 patients encounter physical and emotional problems within the limited healthcare system. The study suggests that comprehensive interventions are needed for nurses. Furthermore, detailed guidelines, strengthening of nursing personnel, and improvements to the nursing system are vital to effectively cope with the pandemic. The government and medical institutions should be aware of the needs of nurses and what they are going through, and make efforts to improve the quality of life of healthcare workers and create a safe healthcare environment.