Acrylamide (AA) is a ubiquitous neurotoxic contaminant. Our objectives were to evaluate associations of internal AA exposure with sleep health outcomes. Data from 2753 adults aged 20-79 years in the National Health and Nutrition Examination Survey (NHANES) was utilized. Internal AA exposure was assessed using hemoglobin adducts and urinary biomarkers. Short sleep duration (SSD) and self-reported trouble sleeping were employed as indicators of sleep health. Markers of systemic inflammation were calculated. Each one-unit increase in ln-transformed hemoglobin adducts of acrylamide (HbAA), hemoglobin adducts of glycidamide (HbGA) and HbAA + HbGA and creatinine-adjusted urinary N-Acetyl-S-(2-carbamoylethyl)-L-cysteine concentration was statistically significantly associated with 1.37-fold (95% confidence interval [CI]: 1.16, 1.62
p = 0.002), 1.41-fold (95%CI: 1.19, 1.68
p = 0.002), 1.43-fold (95%CI: 1.19, 1.70
p = 0.001), and 1.24-fold (95%CI: 1.08, 1.42
p = 0.007) risk in SSD, respectively. The significant associations were strengthened in smokers after stratification by smoking status. Higher AA hemoglobin biomarkers predicted increases in markers of systemic inflammation. In conclusion, internal AA exposure was associated with an increased risk of SSD and elevated systemic inflammation among United States adults. The findings shed light on the potential effects of AA's health threat and future research is warranted to develop intervention strategies.