Changes in the welfare systems including the sickness insurance scheme are ongoing in several countries, and better knowledge on the extent of health problems in sickness absence seems needed. The overall aim of this cross sectional study was to assess and compare self-rated health, common symptoms and mental well-being in two samples of incident sick-leave cases with the general population. The study was performed in Sweden, 2008, and three samples of individuals aged 19–64 years were selected. The final study populations consisted of 3310 consecutive new employer reported sick-leave cases, 498 consecutive new self-reported sick-leave cases and 4027 individuals from a random general population sample. A mailed questionnaire was distributed. Validated questions and instruments on health and demographic data was analysed in bivariate and multivariate analyses. Poor self-rated health, high levels of symptoms and low mental well-being was reported by a significantly higher proportion in the two sick-leave samples compared with the general population. In logistic regressions with the generalpopulation as reference we adjusted for age, income, occupational class and current sick-leave. The fully adjusted OR for poor self-rated health, high levels of symptoms and low mental well-being respectively were 1.54 (95% confidence intervals 1.24–1.91), 1.95 (1.54–2.48) and 1.41 (1.11–1.79) among the employer reported male sick-leave cases and 1.94 (1.34–2.82), 1.76 (1.14–2.70) and 2.11 (1.40–3.17) among self reported male sick-leave cases. Corresponding figures for women were 1.80 (1.56–2.08), 1.42 (1.22–1.66) and 1.21 (1.03–1.43) and 2.10 (1.60–2.75), 1.97 (1.1–2.57) and 1.78 (1.35–2.36). Differences in health problems between the groups remained significant in the fully adjusted model. We conclude that sick-listed individuals have a higher burden of illness also after control for current sick leave than the general population. Consequence analyses of more rigorous legislation and increased demands need to take this into account.