The casualties include at least 6 million fish, thousands of alligators, turtles and river dolphins, scientific reports cited by Nature News said.
Losses of penguins were reported in Brazil and cattle deaths, affected by a cold snap from the Antarctic, hit farmers in Paraguay.
The scientists' version of how the aquatic animals were decimated was hotly contested by visitors to Nature News Web site, while official Bolivian reports on the aquatic deaths were still awaited.
Bolivia is no stranger to extreme weather conditions as its geography interacts with humid tropical conditions but the aquatic deaths took scientists by surprise.
Tens of thousands of Bolivians who depend on the river resources face a bleak future as officials try to work out how to deal with a developing ecological crisis and its impact on the communities and national economy.
The deaths came to light after a sudden cold spell during the Southern Hemisphere's winter, which begins in late June and lasts to the third week of September.
The region around the city of Santa Cruz de la Sierra, in the eastern part of Bolivia, usually experiences warm subtropical climate. Temperatures average 74 degrees Fahrenheit with 68 percent humidity.
Scientists who visited the affected rivers said Bolivia could be facing its worst ecological disaster in recent history. They reported river waters dotted with tens of thousands of dead fish, denying nearby communities access to safe drinking water.
The trouble began after cold Antarctic air settled over the southern cone of South America for most of July.
Water temperature in Bolivian rivers, normally about 59 degrees Fahrenheit, dropped to about 39 degrees Fahrenheit and was matched by the air temperature -- coldest since 36.5 degrees recorded in 1955.
Other experts cited by Nature News said shock caused by extreme cold could cause the mass deaths among fish. "When fish die, it's usually not a single stressor, but multiple stressors interacting," said Steven Cooke, an aquatic ecologist at Carleton University in Ottawa. "So, if cold shock or cooler temperatures are being implicated in mortality, there's probably something else going on as well."
Other experts said pollution from the large-scale burning of farmland around Santa Cruz could also be responsible for aquatic deaths.
Officials said funding was awaited to conduct detailed research into the aquatic deaths. Meanwhile, Bolivians in the affected areas are hoping for government help with the cleaning of the river waters before disease sets in.