Water pollution associated with flooding is one of the major problems in cities in the global South. However, studies of water quality dynamics during flood events are not often reported in literature, probably due to difficult conditions for sampling during flood events. Water quality parameters in open water (canals, rivers, and lakes), floodwater on roads and water in sewers have been monitored during the extreme fluvial flood event on 7 October 2013 in Can Tho city, Vietnam. This is the pioneering study of urban flood water pollution in real time in Vietnam. The results showed that water quality is very dynamic during flooding, especially at the beginning of the event. In addition, it was observed that the pathogen and contaminant levels in the floodwater are almost as high as in sewers. The findings show that population exposed to flood water runs a health risk that is nearly equal to that of being in contact with sewer water. Therefore the people of Can Tho not only face physical risk due to flooding, but also exposed to health risk.