The Gironde estuary is considered the largest South-Western European estuary and covers an area of 625 km2 at high tide. This transition zone between marine and freshwater environments is formed by the junction of the Garonne and the Dordogne rivers. The Gironde is characterized by a strong spatiotemporal variability of environmental parameters, modulating biological response. While most studies deal with the impact of anthropogenic pressures on estuaries, this research aims at understanding and distinguishing the part of variability that can be explained by human local activities from those that is linked to Climate Change. Using data from the ecological monitoring of the Blayais nuclear power plant, this research contributes to better know the estuarine evolution over the last thirty years. This paper presents the chemical, physical and climatic parameters changes by characterizing global and local trends, interannual variability and an eventual periodicity using different data analyses (i.e. linear regression, moving average, and eigenvectors filtering). Then, correlations between environmental parameters were analyzed and the potential influence of climate variability was evaluated with a standardized Principal Component Analysis.