Staff dealing with a variety of major geopolitical issues, from Ukraine to Kashmir, were sent termination notices in the afternoon, said the sources, who requested anonymity as they were not permitted to speak to the media.
The move came just weeks after Secretary of State Marco Rubio took over from Mike Waltz as national security adviser.
The NSC declined to comment.
The NSC restructuring is expected to further reduce the agency's influence, transforming it from a powerful policymaking body into a small organisation focused more on implementing the president's agenda than on shaping it, the sources said.
In practice, the move is expected to grant more authority to the State Department, the Defence Department and other departments and agencies involved in diplomacy, national security and intelligence matters, the sources said.
The administration's aim is to reduce the size of the NSC to just a few dozen people. Four sources with knowledge of the plans said they expect the final headcount at the NSC to come out to around 50 people.
The NSC is traditionally the main body used by presidents to co-ordinate national security strategy. Its staff often make key decisions regarding America's approach to the world's most volatile conflicts and play a key role in keeping America safe.
The body had more than 300 staffers under Democratic President Joe Biden, but even before the recent firings under Trump was well less than half the size of Biden's NSC. The NSC staffers who are cut from the agency will be moved to other positions in government, two of the sources told Reuters.
Many conservatives have long pushed for a pared-down NSC, arguing that a number of the positions are duplicative of functions found elsewhere in the government.
The NSC has had a hard time recruiting top talent in recent months. Certain key positions, like the top post overseeing Latin American affairs, were never filled on a permanent basis.
Several high-ranking staffers were fired earlier in the year after right-wing conspiracy theorist Laura Loomer presented Trump with a list of national security staffers she perceived to be disloyal.
Disclosures that Waltz, the previous national security adviser, had accidentally shared information on an imminent bombing campaign in Yemen with an Atlantic journalist further dented morale.
As part of the restructuring, certain sections of the NSC - known as directorates - are expected to be combined with other directorates or eliminated altogether, three sources said. In most of the directorates that remain, only a few staff are left, the sources added.
Among the directorates that may cease to operate as independent bodies are those overseeing African affairs and multilateral organisations, like NATO, three sources said.
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