This study analyses distinct trajectories of vital exhaustion (VE; a measure of mental health incorporating signs of stress and depression) over a period of 15 years in healthy adults and investigates further the consequences for markers of low-grade inflammation as indicators of cardiovascular disease risk. Data of 341 participants of the Amsterdam Growth and Health Longitudinal Study were utilized. VE was measured by the Maastricht Questionnaire. Markers of low-grade inflammation included interleukin-6, interleukin-8 and tumour necrosis factor-α. Distinct trajectories of VE were obtained by latent class growth models, and consequences for markers of low-grade inflammation of the trajectories were analysed by linear regressions. We found comparable trajectories of VE for men and women; a 'never vitally exhausted' subgroup (16.9% and 25.1%, respectively), a 'stable preclinical VE' subgroup (51.7% and 68.1%) and a 'chronic VE state' subgroup (31.5% and 6.7%). The subgroups had similar levels of the markers investigated. This study is the first to analyse VE longitudinally in healthy adults and indicates that although distinct trajectories of VE were identified, differential consequences for cardiovascular disease risk were unapparent.