STUDY OBJECTIVES:Although cognitive dysfunction is a recognized consequence of untreated obstructive sleep apnea (OSA), the deficit pattern is heterogeneous. Understanding this heterogeneity may identify those at risk of cognitive deficits and guide intervention strategies. To facilitate understanding, we examined whether distinct profiles of neuropsychological performance were present in OSA and, if so, how they are related to other OSA features. METHODS:We studied sleep clinic (n = 121) and community (n = 398) samples with moderate-severe OSA (apnea-hypopnea index ≥ 15 events/h). Attention and memory were assessed using the Cognitive Drug Research system. Sleep was assessed using polysomnography in the clinic sample and dual channel (flow, oximetry) portable monitoring in the community sample. Latent profile analysis was used to determine structure of cognitive clusters. Discriminant function analysis was used to examine associations between nocturnal and diurnal features of OSA and profile membership. RESULTS:Both samples were best characterized by a 3-profile solution: (1) strong thinkers (performed well across most domains and showed greater cognitive reserve); (2) inattentive fast thinkers (strong processing speed but poor ability to maintain attention); and (3) accurate slow thinkers (strengths in maintaining attention but poor processing speed). Profile membership was associated with mean overnight oxygen saturation and cognitive reserve in the clinic sample and the presence of cardiovascular disease and/or diabetes in the community sample. CONCLUSIONS:These findings help explain the diversity of outcomes in previous studies of cognitive dysfunction in OSA by demonstrating that individual differences in cognitive reserve, nocturnal oxygen saturation, and comorbidities affect how cognition is impacted by OSA.