Officials say vets took the decision as the four-metre (13ft) mammal was being moved in a refrigerated truck.
Overnight, rescuers spent nearly six hours lifting the 800kg (1,763lb) whale from the river using a crane and nets.
They had planned to release the animal in the sea but its health deteriorated after failing to eat.
"It is with heavy hearts we announce that the beluga did not survive," Sea Shepherd France conservation group wrote in a Twitter post on Wednesday.
"We are devastated by this tragic outcome that we knew was very likely," it added.