Background Serum levels of high mobility group box-1 protein (HMGB1) are increased in a variety of inflammatory disorders. Obstructive sleep apnea syndrome (OSAS) is associated with inflammation secondary to chronic intermittent hypoxia, but HMGB1 levels in treated and untreated OSAS have not been evaluated. Methods Twenty healthy subjects and 30 subjects with moderately severe or severe OSAS who desired nasal continuous positive airway pressure (CPAP) treatment were enrolled. Serum levels of HMGB1 and nitric oxide derivative (NOx) from peripheral blood samples were measured, and all subjects underwent a sleep study. These studies were repeated 2 months after nasal CPAP treatment in the patients with OSAS. Results In OSAS before nasal CPAP treatment, the serum level of HMGB1 was higher but that of NOx was lower than those levels of normal subjects. The HMGB1 levels correlated negatively with NOx levels in subjects with OSAS. After nasal CPAP treatment, the HMGB1 and NOx returned to normal levels. Conclusion Elevated HMGB1 levels and reduced NOx levels in patients with OSAS normalized after nasal CPAP treatment. Serum levels of high mobility group box-1 protein (HMGB1) are increased in a variety of inflammatory disorders. Obstructive sleep apnea syndrome (OSAS) is associated with inflammation secondary to chronic intermittent hypoxia, but HMGB1 levels in treated and untreated OSAS have not been evaluated. Twenty healthy subjects and 30 subjects with moderately severe or severe OSAS who desired nasal continuous positive airway pressure (CPAP) treatment were enrolled. Serum levels of HMGB1 and nitric oxide derivative (NOx) from peripheral blood samples were measured, and all subjects underwent a sleep study. These studies were repeated 2 months after nasal CPAP treatment in the patients with OSAS. In OSAS before nasal CPAP treatment, the serum level of HMGB1 was higher but that of NOx was lower than those levels of normal subjects. The HMGB1 levels correlated negatively with NOx levels in subjects with OSAS. After nasal CPAP treatment, the HMGB1 and NOx returned to normal levels. Elevated HMGB1 levels and reduced NOx levels in patients with OSAS normalized after nasal CPAP treatment.