The meeting is chaired by Cambodia's Prime Minister Hun Sen and China's Premier Li Keqiang, who are joined by leaders from Thailand, Laos, Vietnam and Myanmar.
The stated goal of the Mekong-Lancang Cooperation forum, which was created by China in 2015, is to promote sustainable development and boost the quality of life for the millions of people living in the Mekong sub-region.
Known as the Lancang in China, the Mekong River is vital to Southeast Asia, where more than 60 million people rely on it and its tributaries for food, water and transport.
Yet the river is also another potential source of regional tensions due to an increasing number of hydroelectric projects that are altering the flow and raising concerns of ecological damage. Vietnam, already locked in conflict with Beijing over territory in the South China Sea, says it is at particular risk of adverse effects.
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China is also seeking to have parts or the river dredged or rapids cleared so that large cargo ships can navigate. Environmentalists have warned this could have dire consequences on the ecosystem.
In the two years since the forum's establishment, China has set aside billions of dollars to support 45 projects including water resource research centers and cooperation on connectivity projects, industrial capacity, border trade, agriculture and poverty alleviation.