The Native Americans had little resistance to diseases newly introduced from Europe.
Spanish suppression of native revolts further reduced the population in northern Florida.
Other escaped slaves joined various Seminole bands as free members of the tribe.
While most of the former slaves at Fort Mose went to Cuba with the Spanish when they left Florida in 1763, others lived with or near various bands of Indians.
By 1707, colonial soldiers from the Province of Carolina and their Yamasee Indian allies had killed or carried off nearly all the remaining native inhabitants, having conducted a series of raids extending the full length of the peninsula.
In the first decade of the 18th century, 10,000 – 12,000 Indians were taken as slaves according to the governor of La Florida and by 1710, observers noted that north Florida was virtually depopulated.
Other Native American groups in Florida during the Seminole Wars included the Choctaw, Yuchi or Spanish Indians, so called because it was believed that they were descended from Calusas; and "rancho Indians", who lived at Spanish/Cuban fishing camps on the Florida coast.
Escaped African and African-American slaves who could reach the fort were essentially free.
Slaves continued to escape from the Carolinas and Georgia and make their way to Florida.
The blacks who stayed with or later joined the Seminoles became integrated into the tribes, learning the languages, adopting the dress, and inter-marrying.
Many were from Pensacola; some were free citizens though others had escaped from United States territory.
The Spanish offered the slaves freedom and land in Florida; they recruited former slaves as militia to help defend Pensacola and Fort Mose.
The few remaining natives fled west to Pensacola and beyond or east to the vicinity of St.