The health crisis caused by COVID-19 has resulted in the physical and emotional deterioration of health personnel, especially nurses, whose emotional state is affected by the high risk of contagion, the high demands of health services, and the exhausting working hours. The objective of this research was to determine the relationship between fear, anxiety, and fatigue of nurses caring for patients with COVID-19 in a second level public hospital in Peru. This study presents a quantitative approach and correlational level, cross-sectional, and non-experimental design. The sample consisted of 145 nurses who attended patients with COVID-19 in health care areas. The results show a significant relationship between fear of contagion and physical-cognitive fatigue (p < 0.001; r = 317) and a significant relationship between generalized anxiety and physical-cognitive fatigue (p < 0.001; r = 480). It is concluded that in this context, both fear of contagion and generalized anxiety are related to physical-cognitive fatigue.