To support accidental spill rapid response efforts, oil spill simulations may generally need to account for uncertainties concerning the nature and properties of the spill, which compound those inherent in model parameterizations. A full detailed account of these sources of uncertainty would however require prohibitive resources needed to sample a large dimensional space. In this work, a variance based sensitivity analysis is conducted to explore the possibility of restricting a priori the set of uncertain parameters, at least in the context of realistic simulations of oil spills in the Red Sea region spanning a two-week period following the oil release. The evolution of the spill is described using the simulation capabilities of Modelo Hidrodinamico, driven by high-resolution metocean fields of the Red Sea (RS) was adopted to simulate accidental oil spills in the RS. Eight spill scenarios are considered in the analysis, which are carefully selected to account for the diversity of meto-cean conditions in the region. Polynomial chaos expansions are employed to propagate parametric uncertainties and efficiently estimate variance-based sensitivities. Attention is focused on integral quantities characterizing the transport, deformation, evaporation and dispersion of the spill. The analysis indicates that variability in these quantities may be suitably captured by restricting the set of uncertain inputs parameters, namely the wind coefficient, interfacial tension, API gravity, and viscosity. Thus, forecast variability and confidence intervals may be reasonably estimated in the corresponding four dimensional input space.