BackgroundThere is a considerable burden of sedentary time in European adults. We aimed to quantify the differences in adiposity and cardiometabolic health associated with theoretically exchanging sedentary time for alternative 24 h movement behaviours.MethodsThis observational cross-sectional study included Luxembourg residents aged 18–79 years who each provided ≥ 4 valid days of triaxial accelerometry (n = 1046). Covariable adjusted compositional isotemporal substitution models were used to examine if statistically replacing device-measured sedentary time with more time in the sleep period, light physical activity (PA), or moderate-to-vigorous PA (MVPA) was associated with adiposity and cardiometabolic health markers. We further investigated the cardiometabolic properties of replacing sedentary time which was accumulated in prolonged (≥ 30 min) with non-prolonged (< 30 min) bouts.ResultsReplacing sedentary time with MVPA was favourably associated with adiposity, high-density lipoprotein cholesterol, fasting glucose, insulin, and clustered cardiometabolic risk. Substituting sedentary time with light PA was associated with lower total body fat, fasting insulin, and was the only time-exchange to predict lower triglycerides and a lower apolipoprotein B/A1 ratio. Exchanging sedentary time with more time in the sleep period was associated with lower fasting insulin, and with lower adiposity in short sleepers. There was no significant evidence that replacing prolonged with non-prolonged sedentary time was related to outcomes.ConclusionsArtificial time-use substitutions indicate that replacing sedentary time with MVPA is beneficially associated with the widest range of cardiometabolic risk factors. Light PA confers some additional and unique metabolic benefit. Extending sleep, by substituting sedentary time with more time in the sleep period, may lower obesity risk in short sleepers.