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Background: Several studies have reported that dietary and serum concentrations of vitamin D and cholesterol are correlated with mild cognitive impairment (MCI) and Alzheimer's disease (AD). However, little is known about whether 25 hydroxyvitamin D [25(OH)D], lipids, and oxysterols are related to cognitive function.Objective: This study sought to explore the relations between 25(OH)D, lipids, oxysterols, and cognitive function.Methods: In this study, about 209 MCI patients and 209 age- and gender-matched healthy controls were recruited from the Shanxi province of China (49.5% male; median [IQR] age: 63 [59-66] y). Serum concentrations of 25(OH)D, lipids, and oxysterols were measured using ultra-performance LC-MS. Cognitive performance was determined via comprehensive mental, verbal, and auditory cognitive tests. Dietary information was collected using a semiquantitative FFQ and 3 consecutive days of 24-h dietary recalls. Logistic regression analyses, Spearman's correlation, and partial correlation analyses were used to explore correlation between the variables.Results: Participants with vitamin D deficiency [serum 25(OH)D <20.0 ng/mL] were 3 times more likely to develop MCI compared to those with adequate vitamin D (≥30 ng/mL) concentrations. The AUC of 25(OH)D was 0.72 and the cut-off was 16.5 ng/mL (sensitivity:  50.3%,  specificity: 84.4%). Serum 25(OH)D concentrations were negatively correlated with total cholesterol (TC) (r = -0.19, P = 0.02), LDL-cholesterol (r = -0.17, P = 0.04), and 24S,25-epoxycholesterol (24S,25-epoxy-CHO) (r = -0.21, P = 0.01). Conversely, the Montreal Cognitive Assessment (MoCA) (r = 0.185, P < 0.001) and symbol digit modalities test (SDMT) (r = 0.11, P = 0.03) scores were positively correlated with serum 25(OH)D concentrations.Conclusion: The study identified significant differences in serum 25(OH)D concentrations between MCI patients and cognitive healthy controls, and there was a correlation between serum concentrations of 25(OH)D, lipids, and oxysterols and cognitive impairment among people. This study was registered at the Chinese Clinical Trial Registry as ChiCTR1900025452. [ABSTRACT FROM AUTHOR]