Objectives <p>This study assesses the seroprevalence of SARS-CoV-2 antibodies (IgM, IgG, and IgA) among asymptomatic and unvaccinated individuals in Osun State, Nigeria, to quantify hidden infections and inform targeted public health interventions.</p> Methods <p>A total of 300 participants from diverse socio-demographic backgrounds were tested using ELISA in this cross-sectional study, conducted between February and May 2021.</p> Results <p>The study revealed a seroprevalence of 58.0%, with notable differences between urban and rural areas, emphasizing the influence of urbanization on virus transmission. No significant associations were found between seropositivity and demographic factors such as age, gender, or occupation, indicating widespread transmission across all groups. However, elevated seroprevalence was observed among married individuals and self-employed workers, suggesting higher exposure in household and occupational settings.</p> Conclusion <p>These findings underscore the urgent need for tailored public health strategies in low- and middle-income countries, with a focus on urban centers, reducing household transmission, and safeguarding informal workers. The alignment of these results with global trends highlights the critical role of local data in shaping effective public health responses. This study calls for targeted interventions, continuous surveillance, and comparative studies to better manage the current pandemic and prepare for future public health crises. The research provides valuable insights into controlling COVID-19 transmission in similar settings, with significant implications for global health strategies.</p>