Background: Nurses dispense direct care in a wide variety of settings and are considered the backbone of the health care system. They often work long hours, face emotional stress, and are at a high risk of psychosocial and somatic illnesses. Nurses sometimes fall sick but work regardless, leading to presenteeism and subsequent risks to quality of care and patient safety due to the increased likelihood of patients falling, medication errors, and staff-to-patient disease transmission. Objective: This study aims to understand presenteeism among frontline nurses and nurse managers in acute, primary, and long-term health care settings and to contribute to the development of future interventional studies and recommendations. Methods: A qualitative study based on online focus group discussions will explore the perceptions of, attitudes to, and experiences with presenteeism among frontline nurses and nurse managers. Using a pilot-tested interview guide, 8 focus group discussions will involve nurses working in acute care hospitals, primary care settings, and long-term residential care facilities in Switzerland’s French-speaking region and Portugal’s Center region. The data collected will be examined using a content analysis approach via NVivo 12 QSR International software. Results: The University of Applied Sciences and Arts Western Switzerland’s School of Health Sciences and the Polytechnic of Leiria’s School of Health Sciences in Portugal have both approved funding for the study. The research protocol has been approved by ethics committees in both countries. Study recruitment commenced in February 2021. The results of the data analysis are expected by September 2021. Conclusions: This present study aims to gain more insight into the dilemmas facing nurses as a result of all causes of presenteeism among frontline nurses and nurse managers in different health care settings. The researchers will prepare manuscripts on the study’s findings, publish them in relevant peer-reviewed journals, exhibit them in poster presentations, and give oral presentations at appropriate academic and nonscientific conferences. Regarding further knowledge transfer, researchers will engage with stakeholders to craft messages focused on the needs of nurses and nurse managers and on disseminating our research findings to deal with the issue of nursing presenteeism.