Objective: To estimate the cost of depression for the adult population in Catalonia (Spain) for 2006. Method: The total adult population of Catalonia for the reference year was close to 6 million. A cross-design synthesis study was conducted, combining "top-down" and "bottom-up" data from secondary data sources, as well as expert opinion (nominal groups). A societal perspective was adopted. Estimates included direct health costs (hospital, primary, specialised and pharmacological care) and the indirect costs derived from the productivity lost due to morbidity and mortality. Sensitivity analyses were carried out for primary and specialised care resource utilisation. A Monte Carlo simulation model was developed to handle the uncertainty of the unit costs of primary care, specialised care and hospital visits. Results: The total annual cost of depression in Catalonia for 2006 was 735.4 million Euros. Of this figure, 21.2% corresponded to direct costs, including 41 million Euros in primary care (5.6%), 8.1 million Euros in mental health specialised care (1.1%), 5.6 million Euros due to hospitalisation (0.8%) and 101.1 million Euros due to pharmacological care (13.7%); and 78.8% to indirect costs due to productivity loss. 3.7 million work days were lost to temporary disability for depression with a cost of 199.6 million Euros (27.1%), and 353.3 million Euros due to permanent disability (48%). Mortality attributed to suicide accounted for 26.9 million Euros (3.7%). The average annual cost of an adult with depression was close to 1800 Euros. Limitations: The heterogeneity of the data sources, the uncertainty in several estimates (i.e. proportion of psychotropic expenditure attributed to the treatment of depression, suicide rate attributed to depression), and the difficulty in disaggregating anxiety and depressive disorders in a number of databases are study limitations. Conclusions: The burden of depression for the Catalan public health system and society as a whole due to the consumption of resources and, more importantly, the loss of productivity is significant. Inefficiencies may be found in the overuse of pharmaceuticals and in the eligibility criteria of disability for work.