OBJECTIVE Evidence suggests that orexin regulates food consumption, glucose metabolism and insulin secretion. Orexin may have a role in the pathogenesis of type II diabetes mellitus, however its role in gestational diabetes mellitus is not known. We aimed to assess maternal serum and cord blood orexin-A (OXA) concentrations in pregnant women with gestational diabetes mellitus (GDM). METHODS Thirty-five pregnant women with GDM and 35 gestational-age-matched healthy pregnant subjects participated in the study. Maternal serum and cord blood OXA levels were measured with enzyme immunoassay at the time of birth. The correlations between maternal serum and cord blood OXA levels, anthropometric and metabolic parameters were also assessed. RESULTS The mean maternal and cord serum OXA (1.16±0.37 and 1.35±0.20ng/mL, respectively) in the GDM group were significantly different from those of the controls (1.58±0.59 and 1.25±0.21ng/mL, respectively). The mean maternal fasting-glucose-to-OXA ratio was significantly higher in the GDM group. In the GDM group, the mean maternal serum OXA levels were similar in the insulin (n=24) and diet (n=11) treated cases, respectively (1.13±0.36ng/mL and 1.21±0.41ng/mL). Maternal serum OXA levels positively correlated with fetal serum OXA and maternal glucose levels. OXA concentrations in maternal serum were negatively correlated with the fasting glucose, fasting insulin and homeostasis model assessment insulin resistance index. CONCLUSIONS Maternal serum OXA levels decrease, and fetal serum OXA levels increase in women with GDM.