Hesitancy against the Covid-19 vaccines cuts across all nations of the world, but this may not be unconnected to the trolls of misinformation and politicization surrounding the Covid-19 science. Findings from this study reveal that 84.7% of the study population lacks adequate information about the Covid-19 vaccines. 50% of the study population is skeptical about the safety of the Covid-19 vaccines. 100% of the study participants make use of the internet and other social media platforms for their sources of news information. 55.3% of the study population would follow the advice of their healthcare workers pertaining to the Covid-19 vaccines. 26.7% of the study population would listen to instructions given by their parents pertaining to the Covid-19 vaccines, while 20.7% of the study population would follow the guidance of their religious leaders respectively. Thus, the main drivers of Covid-19 vaccine hesitancy in Southern Nigeria are a lack of correct information about the Covid-19 vaccines, misinformation on social media platforms, resistance from religious leaders and parents, and a lack of support for the Covid-19 vaccine uptake on the part of healthcare workers. It is, therefore, imperative that in order to overcome the present challenge, the population of Southern Nigeria should be educated on Covid-19 related subjects and engaged with health promotion initiatives. While accepting the Covid-19 vaccines by the hesitant populations in Southern Nigeria is largely dependent upon the attitudes and influences of religious leaders, parents, and healthcare workers, a much larger study is required to fully establish the ramifications of these important findings. Keywords: Covid-19, Healthcare Workers, Immunization, SARS-CoV-2, Southern Nigeria, Vaccine Hesitancy.