High tide combined with high meteorological surge levels and discharges in the Garonne and Dor-dogne rivers in the Gironde estuary (south-west France), may lead to high water levels and flooding near the Blayais nuclear power plant and the city of Bordeaux, with significant economic and social impacts. A global sensitivity analysis (GSA) was performed with a Telemac2D numerical model currently used for operational water level forecasts. The major sources of uncertainties were identified by computing the Sobol' indices for uncertain inputs with an analysis of variance (ANOVA) approach for a 7-day storm event in 2003. The generation of the GSA ensemble of simulations consists of sampling scalar and field random variables: constant and uniform friction coefficients, as well as time-varying hydrological and maritime forcings. The temporal perturbation of time-dependent upstream hydrological and down-Vanessya LABORIE Saint-Venant Hydraulics laboratory, Cerema, 134, route de Beauvais, CS 60039, 60280 Margny Lès Philippe SERGENT Cerema, 134, route de Beauvais, CS 60039, 60280 Margny Lès Compiègne, France stream maritime forcings is assumed to be represented by a Gaussian Process characterized by a correlation time scale calculated from observations. A Karhunen-Loève decomposition was then applied to retain a limited number of eigenmodes. The GSA is performed for 20 random variables using GENCI HPC computational resources for task parallelism and domain decomposition. This requires the use of 250 000 runs for an elapsed simulation time of 101 days on 32768 cores. The performance of the ensemble was assessed with a rank diagram and a reliability curve in comparison to a set of measured water levels at 12 observing stations along the estuary. It was shown that, for this event, the maritime boundary conditions and the Strickler coefficients have a predominant role along the length of the estuary with an influence driven by the tidal cycle. In the upstream fluvial areas, the friction coefficient and hydrological inputs are predominant.