In this retrospective study, the correlation between pre- and post-treatment plasma Epstein-Barr virus (EBV) DNA and circulating immune subsets as well as the prognostic implications was investigated in nasopharyngeal carcinoma (NPC) patients. Patients (n=356) were diagnosed and received comprehensive treatment at the First People's Hospital of Foshan from 2006 to 2010. Pre- and post-treatment plasma EBV DNA load and circulating immune subsets (percentage of CD3+ T cell, CD3+ CD4+ T cells, CD3+ CD8+ T cells, CD19+ B cells and CD56+ NK cells) were analyzed by real-time PCR and flow cytometry. Patient age correlated negatively with CD3+ T cells (r=-0.264, P=0.001) and positively with CD56+ NK cells (r=0.272, P=0.001). Pre-treatment plasma EBV DNA correlated negatively with CD19+ B cells (r=-0.223, P=0.009) and CD4/CD8 ratio (r=-0.177, P=0.047). Patients with low CD19+ B cell had poorer 5-year progression-free survival (PFS) (66.6 vs. 81.8%, P=0.036) and 5-year overall survival (OS) (70.5 vs. 81.5%, P=0.097) than patients with high CD19+ B cells. Low CD19+ B cells was identified as a negative prognostic factor for 5-year PFS (hazard ratio [HR] 0.487; P=0.040), but not for 5-year OS (HR 0.550; P=0.102) in multivariate analysis. Post-treatment plasma EBV DNA was the most important prognostic factor for 5-year PFS (HR 2.983; P=0.006) and 5-year OS (HR 3.927; P<0.001). This study demonstrates the clinical value of circulating CD19+ B cell measurements in NPC patients.