Obstructive sleep apnea (OSA) is associated with dyslipidemia and increased cardiovascular risk. We assessed the effects of apolipoprotein E (APOE) genotype on low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particle size and lipid subclasses (separated by gradient gel electrophoresis) in patients with OSA. Stable patients (n = 181) prospectively recruited underwent full polysomnography. Both LDL particle size and LDL I proportion were reduced from ε3ε3 homozygotes to ε2 carriers and to ε4 carriers (analysis of variance: P = .024; P = .040, respectively); carriers of the ε4 allele of the APOE genotype had significantly lower LDL particle size and LDL I proportion compared to ε3ε3 homozygotes (P < .05 for both comparisons). Insulin resistance increased from patients with no OSA to those with mild-moderate and to those with severe OSA (P < .001). In multivariate analysis, LDL size was independently predicted by APOE genotype, male gender, and the presence of metabolic syndrome (MetS; P = .001, P = .020, P = .027, respectively). The HDL particle size was not affected by APOE genotype. Our data demonstrate that both the ε4 APOE genotype and MetS are independently related to smaller LDL size in patients with OSA.