Nearly all US COVID-19 deaths in recent months were in unvaccinated people, Rochelle Walensky said.
People who haven't been vaccinated are "particularly at risk" of severe disease and death, she said.
Cases and hospitalization are up in counties with low vaccination rates, she said.
Almost all recent COVID-19 deaths in the US were among unvaccinated people, according to preliminary data from the Centers for Disease Control and Prevention.
People who have not been vaccinated "remain susceptible, especially from the transmissible Delta variant, and are particularly at risk for severe illness and death," Dr. Rochelle Walensky, the director of the CDC, told a press briefing on Thursday.
"Preliminary data from several states over the last few months suggest that 99.5% of deaths from COVID-19 in the United States were in unvaccinated people," Walensky said.
Walensky did not give a specific time frame for the data.
The estimate is in line with findings from a June analysis from the Associated Press, which found that only 0.8% of people who died from COVID-19 in the US in May were vaccinated.
Walensky's comments come as the highly transmissible Delta variant is spreading across the country. Estimates published this week from the CDC indicate that the variant makes up more than half of the cases in the US.
"Although we expected the Delta variant to become the dominant strain in the US, this rapid rise is troubling," Walensky said, adding that the variant was surging in pockets of the country with low vaccination rates.
Nationwide, hospitalization and deaths remain far lower than the numbers seen in January, something Walensky credited to a successful vaccination campaign.
But cases and hospitalization are rising in US counties where vaccination rates are low, she said.
Walensky said 173 counties had case rates above 100 per 100,000 people. That's about three times the national average of about 32 cases per 100,000, according to CDC data.
Nine in 10 of those 173 counties had vaccinated fewer than 40% of their residents, she said.
On Tuesday, President Joe Biden proposed changes to the US vaccination campaign, including suggesting a door-to-door vaccination effort.
Walensky also said on Thursday that the authorized vaccines in the US could prevent severe disease, hospitalization, and death from the Delta variant.
Data indicates that two doses of the Pfizer-BioNTech, Moderna, or Oxford-AstraZeneca COVID-19 vaccines are highly protective against Delta.
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