Obstructive sleep apnea (OSA) is associated with increased cardiovascular mortality, and oxidative stress was suggested to play an important role. We hypothesized that the plasma TRX level, a novel oxidative stress marker, is elevated in OSA patients. Plasma TRX and adiponectin levels, which are significantly associated with cardiovascular mortality, were measured in 41 patients with severe OSA before (n = 41) and after (n = 27) nasal continuous positive airway pressure therapy (nCPAP) for 1 month and in 12 subjects without OSA (non-OSA group). The TRX level was significantly higher (p = 0.02) and the adiponectin level was significantly lower (p = 0.02) in the OSA group than in the non-OSA group. After 1 month of nCPAP (n = 27), the TRX level significantly decreased (p = 0.03), and the adiponectin level significantly increased (p = 0.03). Among the 14 patients with untreated OSA, the TRX and adiponectin levels did not significantly change over a 1-month interval. Among the 53 (41 OSA + 12 non-OSA) subjects, the TRX level was positively correlated with the respiratory disturbance index (p = 0.001) and percentage of time with SaO(2) <90% (p = 0.0002). The adiponectin level, but not the TRX level, was correlated with the BMI (n = 53; p = 0.02). Plasma TRX may be a unique marker for evaluating oxidative stress and monitoring the effectiveness of nCPAP in OSA patients.