This study was designed to analyse the serum resistin level in children with postural tachycardia syndrome (POTS) and its clinical significance. Twenty-one children with POTS and 31 healthy children as controls participated in the study. Clinical characteristics, heart rate and blood pressure in the supine and upright positions were monitored and collected during an upright test, and the symptom scoring of POTS patients was recorded. The serum resistin levels of patients in both groups were determined by enzyme-linked immunosorbent assay. The change in serum resistin levels in the POTS group before and after standing, as well as its correlation with symptom scores and change in heart rate after standing, was analysed. Compared with the control group, the serum resistin levels in the POTS group were significantly increased (P < 0.01). The serum resistin levels in the POTS group before and after standing did not differ (P > 0.05). There was a negative correlation between the serum resistin levels and a change in heart rate from the supine to upright position (correlation coefficient = −0.615, P < 0.01). Moreover, serum resistin levels were negatively correlated with symptom scores (correlation coefficient = −0.493, P < 0.05). Serum resistin levels in children with POTS were significantly higher than those in healthy children and negatively correlated with a change in heart rate from the supine to upright position and symptom scores. These results suggest a protective role of increased resistin in the pathogenesis of POTS.