Background: The COVID-19 pandemic has highlighted the importance of preventive measures in controlling disease spread. This study aimed to assess the uptake of COVID-19 preventive measures, identify associated factors, and examine current perceptions of these measures in the Enugu North Local Government Area, Enugu State, Nigeria. Methods: A cross-sectional study was conducted from January to July 2023 among 500 residents aged 18 years and above. Data were collected using a semi-structured questionnaire. Sociodemographic, perception, uptake of preventive measures, and vaccine-related data were analyzed using descriptive statistics. Chi-square tests were used to establish associations between variables. Results: The majority of respondents (80.6%) demonstrated poor perception towards COVID-19, and 61.8% reported poor uptake of preventive measures. Hand washing, wearing nose masks and staying at home during lockdowns were the most frequently adopted measures. Key barriers to preventive measures uptake included water scarcity (39.2%), economic hardship (52.4%), and disbelief in COVID-19’s existence (44.6%). Only 9.4% of respondents had received the COVID-19 vaccine. Significant associations were found between uptake of preventive measures and age, marital status, education level, profession, monthly income, and religion (all p<0.05). Perception towards COVID-19 was significantly associated with uptake of preventive measures (p<0.05). Conclusions: This study reveals low uptake of COVID-19 preventive measures in Enugu North LGA, influenced by poor perception, socioeconomic factors, and infrastructural challenges. These findings highlight the need for targeted public health interventions, improved risk communication, and addressing structural barriers to enhance adherence to preventive measures during future pandemics.