OBJECTIVE: With the outbreak of coronavirus disease 2019 (COVID-19), the workload of the Iran's health-care system along with the Pre-hospital Emergency Service (PHES) increased significantly so that Iranian fledgling emergency system had never experienced such a crisis. With regard to the importance of the function of PHES as the front-line staff of Iran's health system and its role in controlling the recent epidemic crisis, this study was conducted to identify the challenges of PHES function in the face of COVID-19 pandemic. METHODS: The study was conducted with qualitative approach through content analysis in 2021. Semi-structured interviews were used to collect data. Sampling was purposive and continued until data saturation. After 24 interviews, the data were saturated. The extracted codes were thoroughly prepared as a data pool. After encoding all available data, the related codes were categorized into a single theme. After extracting the themes, a network of themes, related to the research topic, was drawn, and then, the relationship between the themes was analyzed. RESULTS: Data analysis undertaken for the qualitative study resulted in the identification of 4 main themes included: challenges related to facilities and equipment, living with uncertainty, professional and organizational capabilities, and burnout. CONCLUSIONS: PHES personnel have an important and key role in providing care to patients during COVID-19 epidemic period. Individual and systemic challenges were among the most important issues in the experiences of these personnel. These challenges require organizational planning and special attention of health policy-makers to maintain the staff's physical and mental health during the pandemic and the possible crises ahead.