Kaposi?s sarcoma (KS) is an uncommon, multifocal and angioproliferative lesion, which demonstrates a poor prognosis. The aim of the present research was to explore the association of HIV viral load, CD4+ and CD8+ counts and the CD4+/CD8+ ratio on the risk of oral Kaposi?s sarcoma (KS) development. A total of 62 patients were retrieved from March 2008 to October 2020 from the files of two oral pathology centres. Clinical, laboratory and follow-up data were retrieved from their medical files. Poisson regression was used to explore the role of history of immunosuppression and its association with oral KS development. A P-value <0.05 was considered significant. Sixty-two patients were included in the present study (32 with oral KS and 30 with no presentation of lesions anywhere on the body). Patients with oral KS presented a mean age of 32.6 years, and male patients were more affected. The hard palate (15 cases; 46.8%) was the main anatomical site affected. The lesions were mostly presented as swellings (13 cases; 40.6%) and nodules (12 cases; 37.5%). Systemic manifestations were also observed, including candidiasis (4 cases; 12.5%), bacterial infection (3 cases; 9.3%), tuberculosis (3 cases; 9.3%), herpes simplex (3 cases; 9.3%) and pneumonia (3 cases; 9.3%). A significant correlation was observed between HIV viral load, CD4+ count and the CD4+/CD8+ ratio with oral KS development. HIV viral load, CD4+ count and the CD4+/CD8+ ratio are associated with oral KS development.