The four-metre male orca was first spotted two weeks ago near the river's mouth, but made its way dozens of miles upstream towards the city of Rouen.
A plan to guide it back to the sea using sound stimuli failed, and experts concluded it was seriously ill.
The authorities had been preparing to euthanise the animal but activists say it died of natural causes.
Environmental campaign group Sea Shepherd tweeted that the orca's corpse was found at 11:48 local time (09:48 GMT) on Monday.
