Floods in the Mekong delta are recurring events and cause substantial losses to the economy. Sea level rise and increasing precipitation during the wet season result in more frequent floods. For effective flood risk management, reliable losses and risk analyses are necessary. However, knowledge about damaging processes and robust assessments of flood losses in the Mekong delta are scarce. In order to fill this gap, we identify and quantify the effects of the most important variables determining flood losses in Can Tho city through multi-variate statistical analyses. Our analysis is limited to the losses of residential buildings and contents. Results reveal that under the specific flooding characteristics in the Mekong delta with relatively well-adapted households, long inundation durations and shallow water depths, inundation duration is more important than water depth for the resulting loss. However, also building and content values, floor space of buildings and building quality are important loss-determining variables. Human activities like undertaking precautionary measures also influence flood losses. The results are important for improving flood loss modelling and, consequently, flood risk assessments in the Mekong delta.