To explore the influencing factors of perceived stress among frontline nurses during COVID-19, and the role of positive psychological capital in anxiety sensitivity and stress perception, so as to provide evidence for reducing the perceived stress of frontline nurses. From December 2021 to January 2022, 475 frontline nurses from 8 hospitals in X city were investigated by general data questionnaire, positive psychological capital, anxiety sensitivity index and perceived stress scale. The results showed that there were significant differences in nurses’ perceived stress in age, working years, professional title and salary. Perceived stress was positively correlated with anxiety sensitivity, negatively correlated with positive psychological capital, and anxiety sensitivity was negatively correlated with positive psychological capital. Anxiety sensitivity can not only directly predict perceived stress, but also negatively affect perceived stress through positive psychological capital. Therefore, during the epidemic prevention and control in COVID-19, nurses can obtain effective stress coping strategies by strengthening their positive psychological capital, thus reducing their anxiety and perceived stress, and better providing high-quality nursing services for patients.