BACKGROUND: The worldwide pandemic of COVID-19 had put enormous pressure on frontline healthcare workers. In December 2022, China released its "10 new measures," signaling the end of the "dynamic zero COVID-19 strategy." This triggered a period of peak infection, which shocked China's healthcare system and affected the mental health of nurses. OBJECTIVE: To explore the anxiety, depression, and social support levels of frontline nurses during the peak period of COVID-19 infection and to identify the main needs and concerns of nurses during this period. DESIGN: A multicenter cross-sectional study. . 18 hospitals of different grades in three cities in Hunan Province from December 21, 2022, to January 10, 2023, the peak period of COVID-19 infection. . A total of 4,160 nurses completed the survey. METHODS: The questionnaire included general information, symptoms, the preparation for nurses, GAD-7, PHQ-9, PSSS, and two open-ended questions investigating nurses' needs and concerns. General linear models were used to analyze the factors influencing anxiety. Hospital preparation for nurses, nurses' needs, and nurses' concerns were categorized and subjected to frequency counts. RESULTS: The median (P25, P75) scores for anxiety and depression among nurses were 7.00 (3, 12) and 8 (3, 12), respectively. Type of hospital, professional title, family structure, isolation staff lounge preparation, ibuprofen preparation, health status of parents, fever, chest distress, dyspnea, cough, insufficient protective equipment, number of children, and PSSS others were the influencing factors of GAD grades. The top 3 needs were free drugs and treatments (78.71%), shift breaks and paid leave (77.66%), and understanding and supports from hospitals and families (75.99%). The first three concerns were the fear of spreading the disease to family members (83.89%), the after-effects of infection (65.67%), and cross-infection with colleagues and patients (61.70%). CONCLUSIONS: Nurses' anxiety was more severe during peak infection period. Overloaded work schedules and insufficient sleep became a common situation. Worries about family members became the main concern of nurses. Managers should make contingency plans for public health emergencies and provide frontline nurses with protective equipment, stress-relieving measures, and a rotation system. More importantly, they should pay attention to the needs of nurses' family members and provide medical and care support. The media should also explain how hospitals operate and carry out their duties during these extraordinary times in order for the public to comprehend the condition of frontline epidemic fighters.