Objectives: The coronavirus disease 2019 (COVID-19) pandemic globally impacted healthcare due to surges in infected patients and respiratory failure. The pandemic escalated nursing burnout syndrome (NBS) across the workforce, especially in critical care environments, potentially leading to long-term negative impact on nurse retention and patient care. To compare self-reported burnout scores of frontline nurses caring for COVID-19 infected patients with burnout scores captured before the pandemic and in non-COVID-19 units from two prior studies.Methods: The descriptive study was conducted using frontline nurses working in eight critical care units based on exposure to COVID-19 infected patients. Nurses were surveyed in 2019 and in 2020 using Maslach Burnout Inventory (MBI), Well Being Instrument, and Stress-Arousal Adjective Checklist (SACL) instruments.Researchers explored relationships between survey scores and working in COVID-19 units.Results: Nurses working in COVID-19 units experienced more emotional exhaustion (EE) and depersonalization (DP) than nurses working in non-COVID units (p= .0001).Pre-COVID nurse burnout scores across six critical care units (EE mean = 15.41; p= .59) were lower than burnout scores in the COVID-19 intensive care units (EE mean = 10.29; p= .74). Clinical significance (p= .08) was noted by an EE subscale increase from low prepandemic to moderate during the pandemic. Conclusion:Pinpointing associations between COVID-19 infection and nurse burnout may lead to innovative strategies to mitigate burnout in those caring for the most critically ill individuals during future pandemics. Further research is required to establish causal relationships between sociodemographic and work-related psychological predictors of NBS.