Background A healthy healthcare system requires healthy healthcare workers. Protecting healthcare workers including nurses against COVID-19 is crucial, and vaccination could be a viable future option. However, vaccine hesitancy remains a global challenge. Nurses, as a trustworthy and creditable source of vaccine-related information, may build public confidence in vaccination. Hence, research on vaccine hesitancy among nurses is warranted. Objectives This study estimated nurses’ influenza vaccination behaviors and intention to receive COVID-19 vaccine when available, and examined their corresponding 5C psychological antecedents (confidence, complacency, constraints, calculation, and collective responsibility). To investigate the impact of COVID-19-related work demands, the mediation effects of work stress on the association between work demands and COVID-19 vaccination intention were also examined. Design Cross-sectional online survey Settings Nurses were invited to participate via the promotion of a professional nursing organization and by personal referrals during the COVID-19 outbreak in Hong Kong between mid-March and late April 2020. Participants 1,205 eligible nurses (mean age = 40.79, SD = 10.47; 90% being female) were included in the analyses. Methods Demographics, influenza vaccination, intention to have COVID-19 vaccine, the 5C vaccine hesitancy components, work stress and COVID-19-related work demands (insufficient supply of personal protective equipment, involvement in isolation rooms, and unfavorable attitudes towards workplace infection control policies) were reported in the survey. Results The influenza vaccine uptake rate and the proportion intending to take COVID-19 vaccine were 49% and 63%, respectively. Influenza vaccination was associated with working in public hospitals and all 5C constructs (more confidence, more collective responsibility and less complacency, constraints, and calculation), whereas stronger COVID-19 vaccination intention was associated with younger age, more confidence, less complacency and more collective responsibility. COVID-19-related demands were associated with greater work stress, and hence stronger COVID-19 vaccination intention. Conclusion The potential uptake rate of COVID-19 vaccine among nurses was suboptimal to achieve herd immunity. The 5C constructs were useful in predicting influenza vaccination and, to a lesser extent, the intention to take COVID-19 vaccine. The uncertain attributes such as effectiveness, side effects, and effective duration of the COVID-19 vaccine may contribute to this discrepancy. With less work stress among nurses in the post-pandemic period, the intention to take COVID-19 vaccine will likely drop. The 5C constructs should be infused in vaccination campaigns. While a COVID-19 vaccine could be ready soon, the nursing profession may not be ready to accept it. More research work is needed to boost the uptake rate. Tweetable abstract Less than two-third of nurses intended to take COVID-19 vaccine when available. While a COVID-19 vaccine could be ready soon, nursing profession is not ready to accept it.