This paper proposes a methodology to project the possible evolution of river flood damages due to climate change, and applies it to mainland France. Its main contributions are (i) to demonstrate a methodology to investigate the full causal chain from global climate change to local economic flood losses; (ii) to show that future flood losses may change in a very significant manner over France; (iii) to show that a very large uncertainty arises from the climate downscaling technique, since two techniques with comparable skills at reproducing reference river flows give very different estimates of future flows, and thus of future local losses. The main conclusion is thus that estimating future flood losses is still out of reach, especially at local scale, but that future national-scale losses may change significantly over this century, requiring policy changes in terms of risk management and land-use planning.