COVID-19 pandemic in children and rising mortality rates in hospitals, led to increasing pressure on healthcare teams. This descriptive-analytical study compared the fatigue and sleep quality of nurses working in COVID-19 and non-COVID-19 wards in children’s hospitals of Tehran in 2021. This descriptive-analytical study compared the fatigue and sleep quality of nurses working in COVID-19 wards with nurses in non-COVID-19 wards in children’s hospitals of Tehran in 2021. The study included 800 nurses working in 6 pediatric wards of affiliated hospitals of Tehran, University of Medical Sciences in children’s hospitals of Tehran. 100 nurses  were selected by   convenience method based on the entry criteria. Data collection tools included a demographic information questionnaire, the Pittsburgh Sleep Quality Index (PSQI), and the Fatigue Severity Scale (FSS). Data analysis was performed using descriptive and inferential statistics in SPSS16. The research revealed a significant statistical difference in sleep quality (p=0.009, f=2.926) and fatigue (p=0.001, f=5.498) between nurses working in COVID-19 and non-COVID-19 wards. Specifically, the fatigue level was 3.42157 higher among nurses in COVID-19 wards compared to their counterparts in other wards. Nurses in COVID-19 wards had higher levels of fatigue and poorer sleep quality compared to nurses in non-COVID-19 wards. indicating the need to take appropriate care to enhance the mental health of pediatric nurses in various crises, especially in COVID-19.