BACKGROUND: The global pandemic of coronavirus disease of 2019 (COVID-19) has led to unprecedented psychological stress on health workers (HCWs). We aimed to assess the psychological impact of COVID-19 on HCWs in comparison to the stress brought on by the Middle East respiratory syndrome coronavirus (MERS-CoV) epidemic in Saudi Arabia. METHOD: Between February 5th and 16th, 2020, 811 health-care workers (HCWs) of a tertiary care teaching hospital were invited to fill a questionnaire regarding concerns and worries about the novel coronavirus pandemic, along with Generalized Anxiety Disorder (GAD-7) Anxiety Severity screening tool. RESULTS: Out of 582 HCWs who completed the survey questionnaire (response rate of 71.8%), about 40% were exposed previously to MERS-CoV infected or suspected patients during a previous hospital outbreak. While there were no COVID-19 cases reported yet in Saudi Arabia at the time of data collection, still, the anxiety level from COVID-19 was significantly higher than that from MERS-CoV or seasonal influenza: 41.1% were more worried about COVID-19, 41.4% were similarly worried about both MERS-CoV and COVID-19, and 17.5% were more stressed by the previous MERS-CoV hospital outbreak. The most frequent concern was transmitting the infection to family and friends (2.71/5) than to themselves only (2.57/5). CONCLUSION: Pandemic and epidemic infectious diseases such as COVID-19 or MERS-CoV impose a significant level of anxiety and stress on healthcare workers who are caring of infected patients, with their main concern being the risk of transmitting the infection to their families or to acquire it themselves. Therefore, optimizing the compliance of healthcare workers with the proper infection prevention and control measures is paramount during the infectious disease outbreak, to ensure their safety, to decrease the likelihood of getting infected or transmitting the infection to others, and consequently to alleviate their psychological stress and anxiety.