In an interview on the BBC's "Sunday Morning," Fauci said U.S. residents "need to be prepared for the possibility" of restrictions being put back into place.
Presenter Sophie Raworth asked if a new infectious COVID-19 variant could lead to future lockdowns and mask mandates.
"I don't want to use the word ‘lockdowns.’ That has a charged element to it. But, I believe that we must keep our eye on the pattern of what we're seeing with infections," he said, noting that the U.S. is currently moving toward normalcy.
"Having said that, we need to be prepared for the possibility that we would have another variant that would come along," Fauci noted. "And then, if things change and we do get a variant that does give us an uptick in cases and hospitalization, we should be prepared and flexible enough to pivot toward going back – at least temporarily – to a more rigid type of restrictions, such as requiring masks indoor."
Cases, hospitalizations and deaths have fallen rapidly in the U.S. since the winter's COVID-19 surge.
Data from the Johns Hopkins Coronavirus Resource Center shows the U.S. reported 42,967 new cases and 985 new deaths in the past day, whereas daily deaths in January exceeded 4,000.
According to the Centers for Disease Control and Prevention (CDC), the highly transmissible BA.2 omicron sub-variant that is spreading across the globe currently makes up 54.9% of cases.
Fauci cautioned that the "same conditions" that appear to be driving the resurgence of cases in Europe are happening in the U.S.
"It's the greater transmissibility of the BA.2, it's the relaxation of restriction, particularly in the context of indoor masking in congregate settings, and also the fact that immunity, due to both vaccination as well as people who have been previously infected, tends to wane with SARS-CoV-2 – particularly with omicron," he said.
Last week, Fauci said he does not expect another major COVID-19 surge.
"I would not be surprised at all, if we do see somewhat of an uptick," Fauci told a Washington Post event. "I don't really see, unless something changes dramatically, that there would be a major surge."
With the administration now out of funds for a fourth COVID-19 vaccine dose, America's pandemic future is murky.
On Tuesday, the Food and Drug Administration (FDA) moved to authorize a second booster of the Moderna and Pfizer-BioNTech COVID-19 vaccines for people ages 50 and older.
The CDC is expected to weigh in on the decision.
The Associated Press contributed to this report.