Background and Objectives: Omentin-1, also known as intelectin-1, is a novel adipokine with anti-inflammatory activities implicated in inflammatory diseases and sepsis. We aimed to explore serum omentin-1 and its kinetics in critically ill patients early in sepsis and its association with severity and prognosis.Materials and Methods: Serum omentin-1 was determined in 102 critically ill patients with sepsis during the first 48 h from sepsis onset and 1 week later, and in 102 age- and gender-matched healthy controls. The outcome of sepsis at 28 days after enrollment was recorded.Results: Serum omentin-1 at enrollment was significantly higher in patients compared to controls (763.3 ± 249.3 vs. 451.7 ± 122.3 μg/L,p< 0.001) and it further increased 1 week after (950.6 ± 215.5 vs. 763.3 ± 249.3 μg/L,p< 0.001). Patients with septic shock (n= 42) had higher omentin-1 compared to those with sepsis (n= 60) at enrollment (877.9 ± 241.2 vs. 683.1 ± 223.7 μg/L,p< 0.001) and 1 week after (1020.4 ± 224.7 vs. 901.7 ± 196.3 μg/L,p= 0.007). Furthermore, nonsurvivors (n= 30) had higher omentin-1 at sepsis onset (952.1 ± 248.2 vs. 684.6 ± 204.7 μg/L,p< 0.001) and 1 week after (1051.8 ± 242 vs. 908.4 ± 189.8 μg/L,p< 0.01). Patients with sepsis and survivors presented higher kinetics than those with septic shock and nonsurvivors (Δ(omentin-1)% 39.8 ± 35.9% vs. 20.2 ± 23.3%,p= 0.01, and 39.4 ± 34.3% vs. 13.3 ± 18.1%,p< 0.001, respectively). Higher omentin-1 at sepsis onset and 1 week after was an independent predictor of 28-day mortality (HR 2.26, 95% C.I. 1.21–4.19,p= 0.01 and HR: 2.15, 95% C.I. 1.43–3.22,p< 0.001, respectively). Finally, omentin-1 was significantly correlated with the severity scores, the white blood cells, coagulation biomarkers, and CRP, but not procalcitonin and other inflammatory biomarkers.Conclusions: Serum omentin-1 is increased in sepsis, while higher levels and lower kinetics during the first week of sepsis are associated with the severity and 28-day mortality of sepsis. Omentin-1 may be a promising biomarker of sepsis. However, more studies are needed to explore its role in sepsis.