We measured HIV RNA in paired cerebrospinal fluid (CSF) and plasma samples in a prospective study of 91 HIV-infected, antiretroviral therapy (ART)-naive patients with cryptococcal meningitis. CSF HIV RNA was lower than in plasma (median 4.7 vs. 5.2 log10 copies/mL, p<0.0001) and positively correlated with plasma HIV RNA, peripheral CD4+ T-cell percentage and CSF CXCL10. Plasma/ CSF ratio of HIV RNA ranged widely from 0.2 to 265.5 with a median of 2.6. CSF quantitative cryptococcal culture positively correlated with CSF CCL2 and CCL3. CSF-plasma viral discordance was not associated with cryptococcal-associated immune reconstitution inflammatory syndrome.