National ecosystem assessments provide evidence on the status and trends of biodiversity, ecosystem conditions, and the delivery of ecosystem services to society. I this study, we analyze the complex relationships established between ecosystems and human systems in Spain through the combination of Driver-Pressure-State-Impact-Response framework and structural equation models. Firstly, to operationalize the framework, we selected 53 national scale indicators that provide accurate, long-term information on each of the components. Secondly, structural equation models were performed to understand the relationships among the components of the framework. Trend indicators have shown an overall progressive biodiversity loss, trade-offs between provisioning and cultural services associated with urban areas vs. regulating and cultural services associated with rural areas, a decoupling effect between material and non-material dimensions of human wellbeing, a rapid growing trend of conservation responses in recent years and a constant growing linear trend of direct or indirect drivers of change. Results also show that all the components analyzed in the model are strongly related. On one hand, the model shows that biodiversity erosion negatively affect the supply of regulating services, while it is positively related with the increase of provisioning service delivery. On the other hand, the most important relationship found in the model is the effect of pressures on biodiversity loss, indicating that response options for conserving nature cannot counteract the effect of the drivers of change. These results suggest that there is an insufficient institutional response to address the underlying causes (indirect drivers of change) of biodiversity loos in Spain. We conclude that more structural changes are required in the Spanish institutional framework to reach 2020 biodiversity conservation international targets.