Background: Vaccination against COVID-19 is one of the global strategies to the containment of the disease. This global effort is being hampered by vaccination hesitancy which is more worrisome in low-resource countries like sub-Saharan Africa. Objectives: The objectives of this study are to evaluate the awareness of COVID-19 disease, COVID-19 vaccine uptake and its determinants in a rural Nigerian setting. Materials and Methods: It is a cross-sectional study of 460 participants recruited at random between 1st August and 30th of September 2021 in a rural hospital in Anambra state, Nigeria. The participants were interviewed using pre-tested structured questionnaire. Data obtained were represented using frequency table, percentages, bar chart, and odds ratio. The level of significance was at P value < 0.05. Results: The majority were aware of COVID-19 disease; and mass media was the major source of information. Seven percent (7.0%) of the participants had received COVID-19 vaccine. A significant number (216/460, 15.9%) were afraid of the vaccine. Reasons adduced for poor uptake included vaccination center being far, cost of transportation, and non-availability of vaccine. Vaccine uptake was significantly affected by participants’ age [aOR= 3.69 95% CI (1.63–13.14); P = 0.044], and a family member being already vaccinated [aOR=11.27 95% CI (1.60–78.78); P = 0.015]. Conclusion: The uptake of COVID-19 vaccine is very low among the study population. This highlights the need for healthcare providers in the study population to reeducate and provide better information to the population on the importance of COVID-19 vaccination.