Worsening the rapidly escalating border dispute over the oil-rich Essequibo region, which Venezuela also claims.
The helicopter was scheduled to transport the officers for an inspection of troops along the Guyana-Venezuela border.
Guyana's Chief of Staff, Omar Khan, stated during a press conference that communication with the helicopter was lost shortly after takeoff in adverse weather conditions. He added that there was "no information to suggest" Venezuela's involvement in the disappearance.
Amid mounting tensions exacerbated by a contentious referendum in Venezuela last weekend, officials from both Guyana and Venezuela agreed earlier in the day to maintain "open channels of communication."
Venezuelan President Nicolas Maduro is advancing his plans to seize the oil-rich Essequibo region, controlled by neighboring Guyana.
Following the referendum, President Maduro ordered the state oil company to issue licenses for extraction there and proposed legislation to make the area part of Venezuela. In response, Guyana has placed its defense forces on high alert.
In a Facebook post, Guyana's President Irfaan Ali mentioned having discussions with the UN Secretary-General and requested the UN Security Council consider intervening.
"This is a direct threat to Guyana's territorial integrity, sovereignty, and political independence. Guyana sees this as an imminent threat and will strengthen precautions to protect its territory," he said.
He also sought to reassure the country's investors, primarily oil companies, about the safety of their investments.
Meanwhile, Brazil announced on Wednesday that its military is reinforcing its presence along the borders with Guyana and Venezuela by deploying more troops and armored vehicles.
Earlier, Sarbaz.kz reported on Venezuela's territorial claims against Guyana.