BACKGROUND Inflammation has been evidenced as a critical contributable mechanism for the atrial fibrillation (AF) onset and development. As the consistent inflammatory and oxidative marker, the effects of white blood cell (WBC) and its differential on lone atrial fibrillation (LAF) were investigated in the study. METHODS A total of 126 patients with paroxysmal LAF who scheduled for rhythm control drug therapy and 120 age- and gender-matched subjects in sinus rhythm were included sequentially. Peripheral blood sample and clinic data were collected during the first evaluation. Recurrence of AF was evaluated by outpatient clinics and telephone visits for the following 12 months. RESULTS Peripheral eosinophil count, neutrophil count, and left atrial diameter (LAD) were significantly higher in LAF than control. Within a follow-up of 12 months, 56 patients (44.4%) had developed AF recurrence. Patients with AF recurrence had higher eosinophil count and LAD. Univariable analyses showed a statistically significant relationship between eosinophil count (P = 0.042), LAD (P = 0.030), and AF recurrence. Multivariate logistic regression analysis showed that LAD (OR: 1.090 per 1 mm increase; 95% CI: 1.007-1.180; P = 0.032) and eosinophil (OR: 1.643 per 1 × 108 /L increase; 95% CI: 1.047-2.578; P = 0.031) were independent predictors of AF recurrence during antiarrhythmic drug therapy. CONCLUSIONS Our results support the association of the WBC response and its components with the LAF. Especially, the peripheral eosinophil and LAD may play important roles in mediating inflammation and atrial remodeling in AF.