An extreme cold exposure event occurred between March 14th and 19th 2011 in northern and central Lao PDR resulting in a major mortality of cattle and buffalo. At least six northern and one central province reported losses, involving 46 districts and 1,384 smallholder farmers, with a total of 7,162 cattle and 3,744 buffalo reported to have died in association with cold weather. Affected animals were observed to shiver, display slow and shallow respiration, lose consciousness and eventually die. Many deaths occurred at night and were recorded in both sexes and all ages of large ruminants. However, mortalities occurred mostly in animals that were free-grazing in the forest and natural grassland, and exposed to the cold weather. Some housed animals that were provided with warmth from shelter and fires and supplementary feed did not die. Samples from dead animals collected for laboratory analysis confirmed that bacterial or viral pathogens were not present. The cause of the mortality was attributed to hypothermia, and the economic losses were estimated at USD 2,463,912.00. Xieng Khouang Province reported the most severe losses with deaths of 4,600 cattle and 1,665 buffalo. At Thong Haihin meteorological station in this province on March 16th and 17th 2011, minimum temperatures recorded were 6.7°C and 7.5°C and rainfall recorded was 36.6 mm and 61.7 mm, respectively. This was the first reported extreme cold event in living memory occurring between the end of dry season and beginning of the wet season in northern Laos. This event is reported in detail as it caused a major loss of wealth for poor smallholder farmers and indicates that strategies to minimise the impact of extreme cold weather events need to be included in livestock development extension programmes.