The move "will meaningfully dent the (Venezuelan) government's cashflow," wrote Risa Grais-Targow, Latin America director at Eurasia Group, a political consultancy.
"PDVSA will have to deeply discount its barrels in order to displace the heavy Middle Eastern crudes that those refineries are currently processing. This will also carry extra transportation costs," she added.
Washington's sanctions are aimed at putting pressure on socialist leader Nicolas Maduro to step aside.
Venezuela was thrust into a political crisis last Wednesday, when opposition leader Juan Guaido declared himself the rightful interim president, prompting world powers including Washington and many Latin American nations to recognize him as the country's "acting president." The move spurred Maduro to break relations with the U.S. and order all American diplomatic personnel to leave the country.
The latest sanctions will transfer control of Venezuela's oil wealth to forces that oppose Maduro and deprive the strongman of resources that could prolong his grip on power.