Background: COPD is associated to increased fatigue, decreased health status and mortality. However, these relationships are rarely evaluated in population-based studies. Aims: To describe the relationship between health status, respiratory symptoms and fatigue among subjects with and without COPD. Further, to evaluate whether fatigue and/or health status predicts mortality in these groups. Methods: Data were collected in 2007 from the population-based OLIN COPD study. Subjects participated in lung function tests and structured interviews, and 434 subjects with and 655 subjects without COPD were identified. Fatigue was assessed by FACIT-Fatigue and health status by the generic SF-36 questionnaire including physical (PCS) and mental (MCS) components. Mortality data until February 2012 were collected. Results: Fatigue greatly impacts the physical and mental dimensions of health status, both among subjects with and without COPD. Among subjects with clinically significant fatigue, COPD subjects had significantly lower PCS-scores compared to non-COPD subjects. Fairly strong correlations were found between FACIT-F, SF-36 PCS and MCS, respectively. In multivariate models adjusting for covariates, increased fatigue, decreased physical and mental dimensions of health status were all associated to mortality in subjects with COPD (OR 1.06, CI 1.02-1.10, OR 1.04, CI 1.01-1.08 and OR 1.06, CI 1.02-1.10), but not in non-COPD. Conclusions: Fatigue and decreased health status were closely related among subjects with and without COPD. Not only physical health status, but also fatigue and mental health predicted mortality among subjects with COPD. Fatigue assessed by FACIT-F, can be a useful instrument of prognostic value in the care of subjects with COPD.