Venezuelan authorities put out a call for their arrest through the international police agency Interpol, judicial police chief Marcos Chavez told The Associated Press on Monday.
He said investigators believe the three had planned to board a private plane on Venezuela's Margarita Island on June 9 that was to carry the drugs to Africa.
Ten suspects have already been detained in the case, including Georges Masudi, a diplomat from the Democratic Republic of Congo, his American assistant Robert Gagnon, a Mexican pilot and co-pilot, five Venezuelan police officers and one airport employee.
Police do not know the whereabouts of the three suspects but have found "elements linking them" to the others detained in the case, Chavez said. He did not identify the Americans.
Justice Minister Pedro Carreno said after the bust that the private plane was stopped by the National Guard on the runway and that the cocaine was seized inside cars on the edge of the runway before it could be loaded into the plane.
Gagnon insisted he and the other foreigners are innocent.
"We didn't commit any crime. There wasn't even a judicial order for us to be detained," Gagnon told the AP by phone from the jail where the men are being held on Margarita Island.
The Mexican co-pilot, Carlos Gaona Salas, said they landed on the island only to refuel since fuel is cheap in Venezuela and it was on the flight path between Toluca, Mexico, and Sierra Leone. He said their final destination was the Congo.
Prosecutors said last month they had seized cash - U.S. dollars, euros, Colombian and Mexican pesos, and Congolese francs - totaling about US$22,000 (EUR 16,500).
Gaona disputed that account, saying the National Guard soldiers opened a suitcase belonging to Masudi carrying US$30,000 (EUR 22,000) and took the money - in addition to US$2,000 (EUR 1,470) from Mexican pilot Jose Fernando Acosta.
The attorney general's office said it would not immediately comment on Gaona's account.