Abstract Rhesus Rhadinovirus (RRV) is closely related to human herpesvirus 8 (HHV-8) or Kaposi’s sarcoma-associated herpesvirus (KSHV). In rhesus macaques (RM) previously inoculated with simian immunodeficiency virus (SIV), RRV infection results in the development of several B cell lymphoproliferative disorders similar to those seen in AIDS patients infected with KSHV. In this study we compared the adaptive immune response to RRV infection generated in both immune deficient (SIV+) and immune competent (SIV-) RM. We evaluated the kinetics and size of the proliferative burst to RRV infection by determining the prevalence of Ki-67+ cells within CD4, CD8b, and CD20 positive subsets. Furthermore, we measured the prevalence of antigen specific T cells in peripheral blood as well as bronchial alveolar lavage. Our data indicates that immune competent animals generate substantially larger CD8 and CD20 responses, albeit with similar kinetics, than immune deficient animals. Furthermore, immune deficient animals show higher viral loads and sustained viremia, suggesting that CD8 and CD20 responses are critical in the initial control of RRV viral growth and spread. Interestingly, antigen specific responses are more easily detected in peripheral blood of immune deficient animals.