Abstract： Objective To investigate the expression of activating receptors (NKG2D and NKp46), inhibitory receptors (NKG2A and KIR) as well as costimulatory molecules (OX40, 4-1BB and ICOS) on peripheral blood natural killer (NK) cells from patients with recurrent genital herpes (RGH). Methods Four-color immunofluorescence staining with flow cytometry was used to detect the expression of NKG2D, NKG2A, KIR and NKp46 in 44 patients with RGH and 40 normal human controls, and to detect the expression of OX40, 4-1BB and ICOS in 29 patients with RGH and 29 normal human controls. Results The proportions of NKG2D-positive and NKp46-positive NK cells significantly decreased in patients with RGH than those in the normal human controls [(93.3 ± 5.4)% vs (96.9 ± 2.5)%, (88.9 ± 8.7)% vs(93.4 ± 4.1)%, respectively, both P < 0.01]. Between the patients and controls, no significant difference was observed in the expression of NK cell inhibitory receptors, NKG2A [(41.8 ± 14.4)% vs (46.0 ± 14.7)%, P > 0.05] or KIR [(68.3 ± 19.1)% vs (69.1 ± 17.6)%, P > 0.05]. A lower expression of costimulatory molecule OX40 was noted in NK cells from patients with RGH compared with those in normal controls [(1.0 ± 1.1)% vs (1.8 ± 1.7)%, P < 0.05]. Conclusions Herpes simplex virus infection could down-regulate the expression of NK cell activating receptors and costimulatory molecules, subsequently suppress the activation of NK cells, and lead to the escape of virus-infected cells from the killing of NK cells.