Fatigue is not only a complex phenomenon accompanying different illness conditions but is also a common complaint among individuals in the general population. Among individuals diagnosed with the chronic neurological disease multiple sclerosis (MS), one-third describe fatigue as the very first symptom, however it is invisible to others. When adopting an action-theoretic approach to health, fatigue may be considered to influence the individual’s goals of life and subjectively perceived health. The aim of this study was to describe perceived fatigue in relation to perceived health among working-aged individuals diagnosed with MS (n = 155), and in a comparative group of individuals randomly selected from the general population living in the same geographical area (n = 190). A self-report questionnaire including the Fatigue Impact Scale, a checklist of six symptoms, questions covering perceived health and levels of and perceptions of fatigue was used for the data collection. The responses on perceived health were dichotomized into two categories: ‘good health’ and ‘ill health’. Of the individuals with MS, 50% graded their perceived health as ill compared with 18% in the reference group (p < 0.001), and 68% graded fatigue as one of their worst symptoms compared with 21% in the reference group. In both groups, higher presence of symptoms and impact of fatigue in daily activities correlated negatively to perceived health. Compared with the individuals in the reference group, the individuals with MS reported higher impact of fatigue in physical areas in both the category of ‘good health’ (p < 0.001) and ‘ill health’ (p < 0.01). The perceived impact of fatigue was mirrored in increased problems in social and family activities. In conclusion, individuals with MS perceive fatigue as one of their worst symptoms three times as often as individuals in the general population. However, individuals with MS probably also adapt themselves or shift in their response to fatigue more than individuals in the general population.