Background Since December 2019, the world has watched the rapid growth of a new pandemic, the COVID-19, a novel pandemic causing death and disruption of normal life. This COVID-19 continues to spread and poses serious threats to public health throughout the world. Even though vaccines are available, there is no guarantee of critical population vaccination, as there still exist stiff resistance to the uptake of the currently available vaccines. Purpose To assess nurses’ perceptions regarding the uptake of COVID-19 vaccines, determine the proportion of nurses vaccinated, as well as the associated factors influencing the uptake of COVID-19 vaccines, so as to alert decision makers on the possible limitations associated with the uptake of the vaccines in the nursing population in Fako Division, Cameroon. Methods This was a mixed method quantitative and qualitative study conducted in Fako Division. A multistage random sampling technique was employed to enroll participants into the study. We collected quantitative data from consented nurses through the use of a structured questionnaire from April 06th to June 2nd, 2022, and qualitative data from nurse leaders through focused-group discussion from June 3rd to 23rd, 2022. In the quantitative phase, we performed descriptive and inferential statistics using the SPSS Version 23.0 and in the qualitative phase, we performed a thematic content analyses and transcription. Results In the quantitative phase, we had more females 131(66.5%), and nurses aged 26-40years 90(45.7%). Most nurses worked in the maternity 49(24.9%). In the qualitative phase, 20(76.9%) were females. Regarding nurses perceptions of COVID-19 vaccines uptake, 133(67.5%) nurses had positive perceptions, and 26(07.6%) had “No trust” in the vaccines. Most nurses 109(55.3%) had not been vaccinated. Negative factors reported by nurses included the belief that the vaccines were dangerous and could cause death 120(60.9%) and 32(16.2%) said no one can influence them to change their minds about taking the vaccines. In the qualitative phase, a majority of the nurse leaders 15(57.7%) wished that COVID-19 vaccination should continue, but with accompanying research to eliminate side effects. It was observed that a majority of the nurse leaders 16(61.5%) had been vaccinated. The respondents reported some factors (belief factors, social influence and lack of knowledge), which had negatively influenced them from taking the COVID-19 vaccines. Conclusion Nurses perceived high relevance for the COVID-19 vaccines while a majority of the nurse leaders perceived that the COVID-19 vaccines are not safe, ineffective with numerous side effects, has a magnetic effect, politically motivated with bad faith, and has the possibility to cause infections. Furthermore, most nurses had not been vaccinated, but a majority of nurse leaders were reported to have taken a COVID-19 vaccine. Several negative factors including belief, social influence and religious factors were reported to have contributed to the lower uptake of the COVID-19 vaccines amongst nurses and nurse leaders in Fako division, Cameroon.