Obstructive sleep apnea syndrome (OSAS) is a common breathing disorder; obesity represents a major risk factor for the development and progression of OSAS although obese patients do not necessarily suffer from OSAS. Adipose tissue communicates with lung in both physiologic and pathologic conditions through the production of adipokines, hormones active in metabolic and inflammatory processes. To explore the extent to which Acrp30 impacts on pathophysiology of OSAS and whether these proteins could be considered as targets for both diagnosis and therapy through enzyme-linked immunosorbent assay, western blotting analysis and fast protein liquid chromatography we have analyzed total levels as well as oligomer distribution in OSAS patients. Our data demonstrated that total Acrp30 serum levels were statistically reduced in OSAS patients compared to controls (p value = 0.02). Within a selected subgroup of OSAS patients with a BMI<30, Acrp30 levels were still statistically lower in OSAS than in control group (p value < 0.05). In addition, more severe patients (AHI>15) exhibited a more pronounced reduction of Acrp30 levels. Interestingly, this reduction is mainly due to a specific decrease of the HMW oligomers, those exhibiting major biological significance. In conclusion, our results strongly suggest a role for Acrp30 oligomerization in OSAS; in fact, the down-regulation of Acpr30 and its HMW oligomers seems to be correlated to illness status independently of concomitant presence of obesity. In addition, this reduction is mainly due to the high-weight oligomers of Acrp30 suggesting a functional role of this adipokine in OSAS.