Obstructive sleep apnea (OSA) is an independent risk factor of multisystem injury including liver and cardiovascular system. Chronic intermittent hypoxia (CIH) associated with recurrent apneas in patients with OSA is one of the most important causes of the increased various systems injury and oxidative stress induced by CIH is an important pathogenic mechanism. Reports indicated that females are less susceptible to oxidative stress injury. The goal of this study was to explore if there exists gender deference of thioredoxin system (Trx/Txnip) alterations by CIH and to clarify a clue for studying gender disparity of OSA-related multisystem injury. C57BL/6J mice of each gender were exposed to CIH with a fractional inspired O2 (FiO2) nadir of 5%. The oxidative and antioxidant biomarkers were evaluated, including serum OxLDL level and Trx/Txnip expression of liver tissue. Male mice exposed to CIH exhibited significant increases in serum OxLDL level than that of the male control (73.24 ± 22.43 μg/dL, 45.20 ± 28.53 μg/dL, P = 0.032) but no significant difference in the females. Male mice exposed to CIH also exhibited decreased expression of Trx than the female (0.4460 ± 0.1023 versus 1.0454 ± 0.1777, P = 0.013) and increased expression of Txnip than the female (0.0123 ± 0.0476 versus 0.0065 ± 0.0058, P = 0.022). These data suggest that CIH induces thioredoxin system change in a gender-specific fashion in mice.