Among mechanically ventilated critically ill adults, the PILOT (Pragmatic Investigation of Optimal Oxygen Targets) trial demonstrated no difference in ventilator-free days among lower, intermediate, and higher oxygen-saturation targets. The effects on long-term cognition and related outcomes are unknown. To compare the effects of lower (90% range, 88-92%), intermediate (94% range, 92-96%), and higher (98% range, 96-100%) oxygen-saturation targets on long-term outcomes. Twelve months after enrollment in the PILOT trial, blinded neuropsychological raters conducted assessments of cognition, disability, employment status, and quality of life. The primary outcome was global cognition as measured using the Telephone Montreal Cognitive Assessment. In a subset of patients, an expanded neuropsychological battery measured executive function, attention, immediate and delayed memory, verbal fluency, and abstraction. A total of 501 patients completed follow-up, including 142 in the lower, 186 in the intermediate, and 173 in the higher oxygen target groups. Median (interquartile range) peripheral oxygen saturation values in the lower, intermediate, and higher target groups were 94% (91-96%), 95% (93-97%), and 97% (95-99%), respectively. Telephone Montreal Cognitive Assessment score did not differ between lower and intermediate (adjusted odds ratio OR, 1.36 95% confidence interval (CI), 0.92-2.00), intermediate and higher (adjusted OR, 0.90 95% CI, 0.62-1.29), or higher and lower (adjusted OR, 1.22 95% CI, 0.83-1.79) target groups. There was also no difference in individual cognitive domains, disability, employment, or quality of life. Among mechanically ventilated critically ill adults who completed follow-up at 12 months, oxygen-saturation targets were not associated with cognition or related outcomes.