Introduction: In addition to anatomical variables, the development of OSA includes staticdynamic pathophysiological factors that cause repetitive obstruction of breathing during the night, resulting in hypoxia and sleep fragmentation. Numerous questionnaires are used in the screening and diagnosis of OSA and the most commonly used are the STOP-Bang questionnaire and the Epworth sleepiness scale. However, the standard diagnostic test for OSA is the all-night polysomnography (PSG), during which sleep and breathing parameters are monitored. AHI, i.e. the number of apneas and hypopneas per hour of sleep, measured by PSG, is a key diagnostic indicator of OSA. However, intermittent desaturations also play a significant role in the development of OSA-related complications, so the oxygen desaturation index ODI is also a relevant indicator of the degree of OSA. As a result of OSA, numerous acute and chronic harmful effects on the body occur. The clinical manifestations of sleep disorders are numerous, and in modern medicine they represent one of the significant public health problems, which is increasingly given strong importance in the research of complex pathophysiology, as well as treatment. Urotensin II is one of the most potent vasoconstrictors that was initially isolated from the fish urophysis. However, further research has shown its expression in humans. UII is a polypeptide with multiple physiological and pathophysiological effects in numerous organ systems, however, it has its most significant effects in the cardiovascular, renal and nervous systems. Circulating UII in human plasma is elevated in a number of psychosomatic diseases, particularly including those closely related to OSA. The main goal of this study was to examine the serum concentration of UII in OSA patients and compare them with the control group. The secondary goals of the study were to examine the relationship between the serum concentration of UII and the severity of OSA and to examine the relationship between the serum concentration of UII and clinical, laboratory and anthropometric characteristics of the subjects. Subjects and procedures: This cross-sectional study was conducted at the Center for Sleep Medicine of University hospital Split and the University of Split Faculty of Medicine in the period from April 2018 to April 2020. The study included 89 subjects with newly diagnosed OSA, and 89 healthy subjects in the control group. In OSA group newly diagnosed OSA was confimed with PSG. The same exclusion criteria as in the OSA group were applied to the control group, with the exception that the OSA screening methods were also applied to the control group (STOP-Bang questionnaire and Epoworth sleepiness scale). Anamnestic data, anthropometric measurements and a clinical examination were taken for both groups. Both the OSA group and the control group had their blood sampled for laboratory tests 7-14 days after the initial examination. Serum UII levels were assessed using an enzyme-linked immunosorbent assay kit for human UII according to the manufacturer's instructions. The latex turbidimetric method was used to determine the level of hsCRP. All other parameters were determined according to standard laboratory practice. Results: A significant statistical difference in hsCRP levels was demonstrated, where the OSA group had a higher level of hsCRP compared to the control group (P < 0.001). A statistically significant difference in the level of serum UII was observed, whereby the OSA group had a higher level of urotensin II in the serum compared to the control group (P < 0.001). Serum UII levels showed a significant but weak positive correlation with body mass index (P= 0.019). A moderate positive correlation of UII with hsCRP (P < 0.001), systolic blood pressure (P < 0.001), and diastolic blood pressure (P < 0.001) was also observed. In the OSA group, UII levels in serum had a significant moderate positive correlation with hsCRP levels (P < 0.001). A moderate positive correlation of serum UII with the ODI index (P < 0.001) and a moderate positive correlation of serum UII and AHI (P < 0.001) were found. The multiple linear regression model showed that systolic blood pressure (P < 0.001), hsCRP (P < 0.001) and AHI (P= 0.013) are positive predictors of UII level in serum. Conclusion: Serum UII levels were found to be significantly higher in patients with OSA compared to healthy control subjects. A significant positive correlation was found with systolic and diastolic blood pressure, hsCRP, and with the AHI and ODI indices. There is a statistically significant difference in the level of UII and the terciles of the AHI and ODI indices, whereby the level of urotensin II is higher at the higher terciles of the AHI and ODI indices. Given that UII concentrations in serum were related to blood pressure, but also to inflammation indices and OSA severity, we can conclude that urotensin II could play an important role in the complex pathophysiology of OSA. Larger longitudinal studies are needed to further elaborate this topic.