Background: Financial crisis and worsened socio-economic conditions are associated with greater morbidity, less utilization of health services and deteriorated population’s health status. The aim of the present study was to investigate the determinants of self-rated health in Greece. Methods: Two national cross-sectional surveys conducted in 2006 and 2011 were combined, and their data were pooled giving information for 10 572 individuals. The sample in both studies was random and stratified by gender, age, degree of urbanization and geographic region. Logistic regression analysis was used to determine the impact of several factors on self-rated health. Results: Poor self-rated health was most common in older people, unemployed, pensioners, housewives and those suffering from chronic disease. Men, individuals with higher education and those with higher income have higher probability to report better self-rated health. Furthermore, the probability of reporting poor self-rated health is higher at times of economic crisis. Conclusion: Our findings confirm the association of self-rated health with economic crisis and certain demographic and socio-economic factors. Given that the economic recession in Greece deepens, immediate and effective actions targeting health inequalities and improvements in health status are deemed necessary.