The two officers, assigned to Malmstrom Air Force Base in Montana, "are being investigated by the Air Force Office of Special Investigations for illegal drug possession," spokeswoman Ann Stefanek told AFP.
The military offered no further details of the case but the news came as US Defense Secretary Chuck Hagel paid a rare visit to an ICBM base in Wyoming.
Hagel's trip follows a series of embarrassing incidents and revelations for the Air Force's nuclear team, including internal reviews signalling morale problems among missile units and the sacking of a number of senior officers.
"In what you do every day, there is no room for error, none. You know that. The American people expect that," Hagel said.
He said Washington would keep up investments to modernise its nuclear arsenal, and that a study was near completion looking at a weapon to replace the Minuteman III intercontinental ballistic missile.
"The United States is going to remain committed, strongly committed, to maintaining a capable and effective, safe, secure nuclear deterrent," Hagel said.
"It is lonely work," he said.
"They do feel unappreciated many times. They're stuck out in the areas where... Not a lot of attention is paid. And I know they wonder more than occasionally if anybody's paying attention."
Officials acknowledged last month that a two-star US general in charge of land-based ICBMs was fired after he went on a drunken bender in Russia, where he repeatedly insulted his hosts.
Air Force Major General Michael Carey lost his job in October after an inspector general found he had displayed "inappropriate behaviour" during the four-day visit to Russia.
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