An improved understanding of sterol and lipid abnormalities in individuals with autism spectrum disorder (ASD) could lead to personalized treatment approaches. Toward this end, in blood, we identified reduced synthesis of cholesterol in families with ≥2 children with ASD participating with the Autism Genetic Resource Exchange (AGRE), as well as reduced amounts of high-density lipoprotein cholesterol (HDL), apolipoprotein A1 (ApoA1) and apolipoprotein B (ApoB), with 19.9% of the subjects presenting with apolipoprotein patterns similar to hypolipidemic clinical syndromes and 30% with either or both ApoA1 and ApoB less than the fifth centile. Subjects with levels less than the fifth centile of HDL or ApoA1 or ApoA1 + ApoB had lower adaptive functioning than other individuals with ASD, and hypocholesterolemic subjects had apolipoprotein deficits significantly divergent from either typically developing individuals participating in National Institutes of Health or the National Health and Nutrition Examination Survey III.