Introduction Physical inactivity and sedentary behaviour are significant modifiable risk factors for chronic diseases, yet their prevalence remains high despite their well-established negative impact on health. This study evaluates regular moderate exercise compared with intermittent vigorous exercise, and their associations with self-rated health, mental health and sleep quality among sedentary and non-sedentary individuals.Methods Participants from the Specchio population-based study in Geneva, Switzerland, completed yearly follow-ups between 2021 and 2024. Baseline information included self-reported physical activity levels and frequency, health and socioeconomic determinants. Follow-ups included information on general self-rated health, new health events, mental health and sleep quality. Logistic regression models were used to evaluate the association between exercise level at baseline (2021) and subsequent outcomes (2021-2024) including general self-rated health, mental health and sleep quality in the overall sample and stratified by sedentary status. Linear regression with fitted models was done by exercise level between 2021 and 2024 for general self-rated health, mental health and sleep quality.Methods Participants from the Specchio population-based study in Geneva, Switzerland, completed yearly follow-ups between 2021 and 2024. Baseline information included self-reported physical activity levels and frequency, health and socioeconomic determinants. Follow-ups included information on general self-rated health, new health events, mental health and sleep quality. Logistic regression models were used to evaluate the association between exercise level at baseline (2021) and subsequent outcomes (2021-2024) including general self-rated health, mental health and sleep quality in the overall sample and stratified by sedentary status. Linear regression with fitted models was done by exercise level between 2021 and 2024 for general self-rated health, mental health and sleep quality.Results Overall, n=5720 participants were included, mean age was 51.2 years. A third of participants reported sedentary behaviour, more likely in young professionals, men, smokers and individuals living with a partner and kids. Older and retired individuals exhibited less sedentary behaviour. Individuals who engaged in intermittent vigorous exercise had higher scores for self-rated health, mental health and sleep quality compared with regular moderate exercise and partial to no exercise. Intermittent vigorous exercise was a determinant for better self-rated health (adjusted OR (aOR) 1.43 (1.18-1.72)) and better mental health (aOR 1.77 (1.47-2.13)). Intermittent vigorous activity remained associated with favourable health outcomes including self-rated health aOR 1.25 (1.03-1.52) and mental health aOR 1.39 (1.17-1.66) in sedentary individuals.Conclusion Intermittent vigorous exercise could be a good option that primary care physicians can recommend especially for young professionals with a busy schedule and increasing sedentary behaviour.