The CNS involvement is frequently found in human immunodeficiency virus (HIV) infection. The purpose of our study was to determine whether proton magnetic resonance spectroscopy (MRS) could detect early brain involvement in neurologically asymptomatic HIV-infected patients with normal MR imagings and to find the correlation between MRS and the immune status. We performed MRS in 30 HIV seropositive neurologically asymptomatic patients with normal MRI and compared the MRS findings with 13 controls. A statistically significant reduction in N-acetylaspartate (NAA)/creatine (Cr) and N-acetylaspartate (NAA)/choline (Cho) in both centrum semiovale (p < 0.005) and thalamic areas (p < 0.05) was found. There is no statistically significant difference as to choline (Cho)/creatine (Cr) and myoinositol (mI)/creatine (Cr) ratios in both regions. The difference of NAA/Cr was more pronounced in the white matter than in the gray matter. As for the immune status, there was a trend towards correlation between CD4 counts and NAA/Cr but devoid of statistical significance. Our results suggest that MRS is more sensitive than conventional MR imaging in detecting CNS involvement in neurologically asymptomatic HIV patients and may, therefore, be used for early detection of brain damage induced by HIV.