Fluvial systems have been considered from a holistic perspective as one of the most important ecosystems given their capacity to provide ecosystem services that directly affect human well-being. To the best of our knowledge, there are no previous national studies that link the complex ecological and social components of fluvial systems, and that analyze their current capacity to supply services, the direct and indirect causes that affect their integrity, and the policy response options taken. We used the Driver-Pressure-State-Impact-Response (DPSIR) framework to explore the complex interlinkages between fluvial ecosystems and social systems in Spain. We selected 58 national-scale indicators that provide long-term information and allowed us to explore the trends and associations among DPSIR components. The trend analysis showed progressive aquatic biodiversity loss and deterioration of regulating services, and an increasing linear trend of direct pressures and indirect drivers, and of institutional responses, to correct negative impacts. Although we were unable to establish the causalities among the DPSIR components with the correlations analysis, we show that most are strongly related; e.g., biodiversity loss and regulating services are negatively associated with the supply of provisioning services and institutional responses, respectively. This indicates that current water management policies do not deal with the underlying causes of ecosystems deterioration. These results suggest that the second Water Framework Directive (WFD) phase could include the ecosystem service concept in its reporting system to better assess aquatic biodiversity conservation and the supply of services delivered by fluvial ecosystems to human well-being.