Background: The pathogenesis of postural tachycardia syndrome (POTS) remains unclear. This study aimed to explore the changes and significance of sulfur dioxide (SO2) in patients with POTS. Methods: The study included 31 children with POTS and 27 healthy children from Peking University First Hospital between December 2013 and October 2015. A detailed medical history, physical examination results, and demographic characteristics were collected. Hemodynamics was recorded and the plasma SO2was determined. Results: The plasma SO2was significantly higher in POTS children compared to healthy children (64.0 ± 20.8 μmol/L vs. 27.2 ± 9.6 μmol/L, respectively, P < 0.05). The symptom scores in POTS were positively correlated with plasma SO2levels (r = 0.398, P < 0.05). In all the study participants, the maximum heart rate (HR) was positively correlated with plasma levels of SO2(r = 0.679, P < 0.01). The change in systolic blood pressure from the supine to upright (ΔSBP) in POTS group was smaller than that in the control group (P < 0.05). The ΔSBP was negatively correlated with baseline plasma SO2levels in all participants (r = ?0.28, P < 0.05). In the control group, ΔSBP was positively correlated with the plasma levels of SO2(r = 0.487, P < 0.01). The change in HR from the supine to upright in POTS was obvious compared to that of the control group. The area under curve was 0.967 (95% confidence interval: 0.928–1.000), and the cutoff value of plasma SO2level >38.17 μmol/L yielded a sensitivity of 90.3% and a specificity of 92.6% for predicting the diagnosis of POTS. Conclusions: Increased endogenous SO2levels might be involved in the pathogenesis of POTS.