The MH-60S Knighthawk was flying with the guided missile destroyer USS William P. Lawrence, part of a carrier group dispatched to the region to increase pressure on Syria.
The US Fifth Fleet said the helicopter was not downed by enemy fire, but ditched into the sea.
Three of the crew members were “accounted for and stable,” said the US Fifth Fleet, which oversees naval operations in a wide area along the Gulf, the Red Sea, the Gulf of Oman and parts of the Indian Ocean.
In a statement, it said six ships, several helicopters and airplanes were involved in the search and rescue effort for the two missing crew members.
“The crash was not due to any sort of hostile activity,” US Naval Forces Central Command, which shares a commander and headquarters with the Fifth Fleet, said in a statement.
“The incident is under investigation.”
The ships involved in the search and rescue effort are the USS William P. Lawrence, USS Nimitz, USS Princeton, USS Shoup, USS Stockdale and USNS Rainier.
The Nimitz and its escorts recently finished a deployment in the Gulf and were diverted to the Red Sea as US vessels deploy off Syria to support possible strikes against Bashar al-Assad’s chemical-armed regime.