BackgroundMedically Unexplained Symptoms (MUS) are frequently encountered in general practice. However, little is known whether MUS affects labor market participation. We investigated the prospective association between MUS at baseline and risk of long-term sickness absence (LTSA), unemployment, and disability pensioning in a 5-year-follow-up study.MethodsIn the Danish Work Environment Cohort Study 2005, 8187 randomly selected employees from the Danish general population answered a questionnaire on work and health. Responses were linked with national registers on prescribed medication and hospital treatment. Participants were classified with MUS if they: a) had reported three or more symptoms during the last month, and b) did not have a chronic condition, neither in the self-reported nor the register data. We assessed LTSA, unemployment, and disability pensioning by linking our data with National registers of social transfer payments.ResultsOf the 8187 participants, 272 (3.3 %) were categorized with MUS. Compared to healthy participants, participants with MUS had an increased risk of LTSA (Rate ratio (RR) = 1.76, 95 % CI = 1.28–2.42), and of unemployment (RR = 1.48, 95 % CI = 1.02–2.15) during follow-up. MUS participants also showed an elevated RR with regard to risk of disability pensioning, however this association was not statistically significant (RR = 2.06, 95 % CI = 0.77–5.52).ConclusionMUS seem to have a negative effect on labor market participation defined by LTSA and unemployment, whereas it is more uncertain whether MUS affects risk of disability pensioning.