Objective:To explore the changes of serum levels of copeptin and α-amylase and their correlations with sleep and cognition in patients with chronic insomnia (CI).Methods:From September 1, 2018 to May 31, 2019, fifty CI outpatients or inpatients from the Department of Sleep Disorder, Affiliated Chaohu Hospital of Anhui Medical University, were enrolled continuously, and thirty good sleepers from the Physical Examination Center of the hospital, were also enrolled to serve as controls. Pittsburgh Sleep Quality Index (PSQI), polysomnography (PSG) and Pre-Sleep Arousal Scale (PSAS) were used to assess the insomnia severity and sleep disorder susceptibility. Montreal Cognitive Assessment scale (MoCA) and Nine-Box Maze were used to respectively assess general cognition and memories. The serum levels of copeptin and α-amylase were detected using enzyme linked immunosorbent assay.Results:Compared to the controls, the CI patients had increased PSQI score (16.0 (15.0, 17.0) vs 4.0 (2.8, 6.0); Z=-7.678, P<0.001) and PSAS score (33.0 (30.0, 37.5) vs 17.0 (16.0, 18.5); Z=-7.350, P<0.001), decreased MoCA score (24.1±2.5 vs 26.7±1.9, t=-4.625, P<0.001), increased numbers of errors in the object working (1.0 (0, 1.0) vs 0 (0, 1.0), Z=-2.099, P=0.036), spatial working (2.0 (1.0, 4.0) vs 1.0 (0, 2.0), Z=-3.935, P<0.001) and object recognition (1.0 (0, 2.0) vs 0 (0, 0), Z=-2.266, P=0.023) memories, and elevated serum levels of copeptin ((35.1±19.9) pg/ml vs (14.8±6.9) pg/ml, t=5.414, P<0.001) and α-amylase ((990.1±193.7) U/L vs (728.9±230.5) U/L, t=5.597, P<0.001). In the CI patients, the level of copeptin was positively correlated with PSQI score ( r=0.338, P=0.013), PSAS score ( r=0.316, P=0.021), sleep latency ( r=0.324, P=0.018), number of awake ( r=0.325, P=0.017) and stage 1 percent of non-rapid eye movement sleep ( r=0.278, P=0.044), and negatively correlated with stage 2 percent of non-rapid eye movement sleep ( r=-0.279, P=0.043); α-amylase was positively correlated with numbers of awake in PSG ( r=0.293, P=0.033). Multiple linear regression analysis showed that copeptin level affected PSQI score (β=0.255, P=0.043) and sleep latency (β=0.254, P=0.043). Conclusion:The levels of copeptin and α-amylase in CI patients elevate, and copeptin may be associated with initial sleep difficulties, but not with cognitive ability, in patients with CI.