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Aim and Objective: The purpose of this study was to generate a conceptual definition and theory of grief for nurses working on the frontlines during the COVID-19 pandemic using grounded theory methodology., Background: The COVID-19 pandemic has had a negative impact on nurses working on the frontlines. The increasing flow of diagnosed COVID-19 cases, diverse unknowns and demands in the treatment of patients with COVID-19, and depression related to countless deaths can trigger grief experiences., Design: A mixed methods approach, including the qualitative method of grounded theory and a quantitative 30-question survey, was used in this study., Methods: Eight focus group sessions were conducted with registered nurses working on the frontlines during the pandemic. Sessions were audio recorded and analysed using constant comparative data analysis. Following the interviews, a survey including demographics and self-report inventories was completed by participants. The COREQ checklist was used to assess study quality., Results: Major concepts that emerged include 'facing a new reality', 'frustrations', 'stress' and 'coping'. Core concepts were combined into a conceptual definition of grief and a grounded theory of the experience of nurses working on the frontlines during the pandemic. Cross comparisons of qualitative and quantitative findings were made and compared with the literature., Conclusions: This study provides a better understanding of the grief experience of nurses working on the frontlines during the COVID-19 pandemic. It is necessary to recognise professional grief and develop intervention strategies that lead to grief reconciliation., Relevance to Clinical Practice: Findings provide useful insights for healthcare administrators to provide support and develop interventions to reduce frustrations and stress of frontline registered nurses., Patient or Public Contribution: This study design involved registered nurses participating in focus group sessions. Participants detailed their experience working on the frontlines of the COVID-19 pandemic with patients, family and hospital administration., (© 2022 John Wiley & Sons Ltd.)