A researcher seems to have pretty good evidence that much of the post-conquest depopulation of Mexico was due not to smallpox and other old-world diseases, but hemorrhagic dever. This does not mean “maybe the Spaniards get off the hook.” It probably makes them more culpable:
[Acuña-Soto] also thinks he may have solved one of the other great mysteries of cocolitzli—namely, why it hit the Aztecs hard but left the Spanish largely unaffected.
Hemorrhagic viruses affect human populations that are already stressed, Acuña-Soto says. “The natives were poor and probably near starvation and living in unsanitary conditions where the rats would congregate. They also worked in the fields, where they’d be exposed to the rat droppings. The Spanish made up the upper classes.”
There is a tiny hint that hemorrhagic fever could have played a role in the depopulation of the Americas post-1491 but before substantial European contact (my extrapolation and emphasis):
The evidence from the Douglas firs shows that during the 16th century central Mexico not only lacked rain but also suffered the most severe and sustained drought in 500 years, one that encompassed nearly the entire continent.
(Acuña-Soto thinks hemorrhagic fever outbreaks are related to conditions immediately following severe drought.)