Chemokine receptors CCR5 and CXCR4 are of major importance in the pathogenesis of HIV-1 infection because they are co-receptors for human immunodeficiency virus (HIV) entry. We examined the frequency of CD3-CD56+CCR5+ and CD3-CD56+CXCR4+ in HIV-infected long-term slow progressors (SPs), HIV typical progressors (TPs) with or without highly active antiretroviral therapy (HAART), and HIV-seronegative controls. The results showed that the frequency of CD3-CD56+CCR5+ was up-regulated, and frequency of CD3-CD56+CXCR4+ was down-regulated in HAART-naïve HIV TPs group compared with HIV SPs group and HIV-seronegative controls (P < 0.05). The frequency of CD3-CD56+CCR5+ was down-regulated by HAART therapy (P < 0.05). The frequency of CD3-CD56+CCR5+ was lower in HIV SPs compared with controls (P < 0.05). Lower frequency of CD3-CD56+CXCR4+ and higher frequency of CD3-CD56+CCR5+ positively correlated with the level of HIV viral loads and negatively correlated with CD4 T cell counts (P < 0.05). These results indicated that the expression of chemokine receptors on NK cells correlated with HIV disease progression. Chemokine receptors CCR5 and CXCR4 are of major importance in the pathogenesis of HIV-1 infection because they are co-receptors for human immunodeficiency virus (HIV) entry.