OBJECTIVE: Through a causal framework, we aim to assess the association between weight change and daytime sleepiness, and the role of obstructive sleep apnoea (OSA) in this relationship. METHODS: From the Sleep Heart Health Study, we selected individuals who were: (1) 40-64 years old, with (2) body mass index (BMI) ≥18.5 kg/m2, (3) no history of stroke, treatment for OSA, and tracheostomy at baseline. We used multiple linear regression to assess the relationship between five-year weight change and daytime sleepiness (assessed through Epworth Sleepiness Scale (ESS)) at five years, adjusting for daytime sleepiness, demographics, diabetes, subjective sleep duration, sleep disturbance, smoking status, weight, and use of antidepressants and benzodiazepines at baseline, in those with complete data (N = 1468). We further assessed the potential mediating role of OSA in this relationship. RESULTS: At baseline, the study participants were on average 55 years old, 46% males, with mean BMI 28 kg/m2; and 25% had ESS>10. ESS at five years worsened by 0.36 units (95% confidence interval (CI) 0.12-0.61, p = 0.004) with every 10-kg weight gain. When stratified by sex, this relationship was only found in women (0.55, 95% CI 0.25-0.86, p < 0.001; p-interaction = 0.02). Approximately one-fifth of the relationship between weight change and daytime sleepiness was mediated by severity of OSA at five years. CONCLUSION: Weight gain has a detrimental effect on daytime sleepiness, mostly through pathways other than OSA. This study provides further evidence and understanding of the relationship between obesity and excessive daytime sleepiness. Copyright © 2017 Elsevier B.V. All rights reserved.