"We don't have certainty, and there is significant evidence that this came from the laboratory. Those statements can both be true," the former CIA chief told reporters when pressed on his statements.
"The American people remain at risk because we do not know ... whether it began in the lab or whether it began someplace else," he said.
"There's an easy way to find out the answer to that - transparency, openness - the kinds of things that nations do when they really want to be part of solving a global pandemic."
Pompeo has been at the forefront of bringing into the mainstream a theory that the SARS-CoV-2 virus slipped out of the Wuhan Virology Institute, which researches some of the world's deadliest diseases.
The World Health Organization has called Pompeo's claims "speculative" and the US government's own top epidemiologist said in an interview this week that all evidence so far "strongly indicates" a natural origin.
Until the speculation on the lab, most scientists believed the virus emerged from a meat market in Wuhan that butchered exotic animals.