Vaccines are critical in the control and prevention of infectious diseases’ transmission. The COVID-19 vaccine is a new innovation, for a relatively new virus. Therefore, in rolling it out, the government should bear in mind the Diffusion of Innovation theory, which places people on a spectrum, ranging from those who are open to innovation and those who are more conservative. Just as with the general public, nurses develop confidence at different rates and may be susceptible to misinformation about vaccines. This study aimed at appraising nurses’ perceptions and attitudes towards COVID-19 vaccines. We conducted a cross-sectional study in September 2021 at a sub-county hospital in Nyamira County, Kenya. Eligible nurses completed structured self-administered questionnaires anonymously. The Statistical Package for Social Sciences (SPSS), version 22, was used to code, enter, analyse, organize, present and store data from the study. Logistic regression was performed to test if perceptions and attitudes had any association with uptake of Covid-19 vaccine. The results showed that all the perceptions and attitudes were positively associated with uptake of Covid-19 vaccine except vaccine safety and the importance of the vaccine to one’s health. The study concluded that there was poor perceptions and negative attitudes towards COVID-19 vaccines which were significant factors for refusal to get vaccinated. It is therefore recommended that the management authorities and stakeholders should promote positive perceptions and attitudes through instituting targeted vaccination campaigns to improve the level of COVID-19 vaccine knowledge among the nurses in particular, and all health care workers in general, in order to achieve a better coverage among them, as well as to influence the patients, clients, their relatives, as well as the general public for ultimate positive vaccine acceptance and uptake.