There were deep aftereffects of the bloody path Soto’s army carved through the Southeast for both the Native Americans living there and the Spanish who claimed it.
For the Natives, the series of military defeats and losses of fighting-age men destabilized political relationships as traditional enemies easily attacked and defeated them. Also, an invisible killer had been let loose: germs and viruses of European diseases such as smallpox and measles. This deadly combination began the long decline of Native Americans and their traditional way of life in the Southeast.
For the Spanish, the Soto expedition had claimed a huge region for La Florida, literally all of Southeastern North America, which meant long-term costs for settling and control. It was also clear that the Natives would not be subjugated by force.
These two factors caused a change in Spanish colonial policy in 1542 ending military conquests and starting traditional colonial settlements and peaceful relations with local indigenous groups.
