Two of the deaths resulted from trees falling on homes, according to local media and authorities.
Authorities in Florida had received no search and rescue requests shortly after landfall early on Saturday, in a sign of limited impact, Governor Ron DeSantis said.
But hazardous conditions remained and storm surges, flash flooding, damaging winds and a risk of tornadoes across parts of the US Southeast were expected, the National Hurricane Center said.
The tornado threat is expected to continue on Saturday across parts of the Florida Panhandle, Georgia and the Carolinas, the NHC said.
In Florida, power restoration was marked as a priority, authorities said, while highways, bridges and airports were reopening, and teams were assessing the damage.
"They're going to make assessments this morning, and I think that'll give us a good sense about the future for the rapidity of the power restoration," DeSantis told a press conference in Tallahassee.
Some 16,000 utility linemen had prepared to respond to the storm, he said.
About 420,000 customers in Florida, 190,000 in Alabama, 43,000 in Georgia and 17,000 in Mississippi had no power as of midday Saturday, according to tracking firm PowerOutage.us.
Alabama's emergency management agency said the downed trees and power lines made travel hazardous in Houston County, which is under a flash flood warning.
"Due to the impacts of Hurricane Isaias, all Houston County roads are closed until further notice," it posted on X.
A category 2 hurricane when it hit Florida's coast and the first of the 2026 Atlantic season, Isaias is expected to produce gusty winds well inland before weakening below gale force later on Saturday, the NHC said.
On Saturday, oil and gas producer Shell said it was beginning to redeploy personnel to its Mars, Olympus, Ursa, Vito and Appomattox assets in the Gulf, whileChevron was advancing efforts to redeploy staff to its platforms and seeking to restore full production.
"Remobilization of crews will continue through Sunday," it said.
Despite the progress, about 69 per cent of oil output and 57 per cent of natural gas production in the US Gulf of Mexico remained shut on Saturday, slightly down from Friday numbers, the Marine Minerals Administration said.
Some 113 production platforms representing 30 per cent of the total remained evacuated, according to the agency.
President Donald Trump, asked about hurricane preparations on Friday, told reporters outside the White House that it was "under control".
The US Energy Department said on Saturday it authorised an emergency exchange of up to four million barrels of crude oil from the Strategic Petroleum Reserve to address supply disruptions due to the hurricane.
