•High CD4 count does not necessarily protect against aggressive AIDS-defining diseases, particularly, HIV-associated Kaposi sarcoma.•Extremely elevated HHV-8, HIV, and EBV viral loads could predict aggressive HIV-associated KS disease course.•Anemia and thrombocytopenia in HIV/AIDS could be autoimmune like ITP and AIHA or bone marrow infiltration-related, by Kaposi sarcoma, for instance, or both. Bone marrow infiltration by Kaposi sarcoma (KS) in human immunodeficiency virus (HIV) patients is rare, with only a few cases reported in patients with a CD4 count greater than 200 cells/ml. To the best of our knowledge, this is the first reported case of bone marrow involvement in HIV-associated KS in which the CD4 count is greater than 400 cells/ml. In this article, we present a patient with HIV-associated KS with skin, lymph node, bone, pulmonary, gastrointestinal, and bone marrow involvement despite a high CD4 count. This is the highest CD4 count associated with bone marrow invasion in the medical literature. A high CD4 count does not protect untreated HIV patients against aggressive, diffuse KS-related lesions, including bone marrow infiltration.