Cryptococcal antigenemia is a significant opportunistic infection among HIV-positive individuals, contributing to high morbidity and mortality if not detected early. This study aimed to determine the burden of cryptococcal antigenemia (CrAg) among antiretroviral therapy-na¨ıve patients with CD4 counts below 200 cells/mm3 at Central Hospital, Agbor, Nigeria. A cross-sectional hospital-based study was conducted, utilizing the lateral flow assay for CrAg detection. Of the 188 participants, 127 (67.6%) were female, and 61(32.4%) were male, with a mean age of 37.37 ± 12.01 years. The prevalence of CrAg positivity was 4.3% (95% CI: 1.50%–7.39%), with 2 males (3.3%) and 6 females (4.7%) testing positive. Although CrAg positivity was higher in females, the difference was not statistically significant. As a precursor to cryptococcal meningitis, a leading cause of mortality in HIV-infected individuals, early CrAg detection can enable timely intervention to reduce disease progression and improve outcomes. This study underscores the importance of routine CrAg screening in high-risk HIV populations to mitigate the burden of cryptococcal disease.