Nurses exposed to coronavirus disease 2019 (COVID‐19) are psychologically stressed. This study examines the characteristics and distribution of negative emotions among Chinese nurses during the COVID‐19 pandemic and explores regulatory emotional self‐efficacy (RESE) as the underlying mechanism in the relationship between nurses' personalities and negative emotions. A cross‐sectional design with convenience sampling was utilized. Three comprehensive tertiary hospitals located in China were selected. Nurses (
n
= 339) who cared for COVID‐19 patients were enrolled. Recruitment was conducted between 14 February 2020 and 1 March 2020. Self‐reported questionnaires about personality, RESE, and epidemic‐related negative emotions were completed online. A correlation analysis, structural equation modelling, and the bootstrapping method were used to analyse the data. This study identified a 24.9% incidence of negative emotions in nurses. RESE was a significant mediator explaining the effect of personality on epidemic‐related negative emotions. RESE mediated the effect of introversion–extroversion on depression (β = −0.151,
P
= 0.015), neuroticism (β = −0.182,
P
= 0.007), fear (β = −0.142,
P
= 0.006), anxiety (β = −0.189,
P
= 0.015), and hypochondria (β = −0.118,
P
= 0.010); it also mediated the effect of neuroticism on depression (β = 0.313,
P
= 0.002), neuroticism (β = 0.394,
P
= 0.003), fear (β = 0.345,
P
= 0.005), anxiety (β = 0.384,
P
= 0.003), and hypochondria (β = 0.259,
P
= 0.004). Nurses caring for COVID‐19 patients displayed negative emotions, particularly emotionally unstable and introverted nurses with a low RESE level. RESE is often essential for interventions because it significantly influences the relationship between personality and negative emotions. In the event of a major outbreak, tailored psychological well‐being education, which includes emotional self‐efficacy strategies, should be provided by organizations to help nurses manage stress related to the outbreak.