Navy officials concluded, given the time elapsed since the incident Saturday, survivability was extremely unlikely, the U.S. Naval Forces Central Command said in a release.
Three of the five crew members were rescued.
The location of the crash site is known; a broad area was searched multiple times by various ships and aircraft, naval officials said.
The Knighthawk helicopter, attached to Helicopter Sea Combat Squadron 6, crashed in the central Red Sea Saturday while attempting to land on the deck of the guided-missile destroyer USS William P. Lawrence.
It was unclear whether the helicopter was trying to take off or land when the accident occurred, NBC News reported at the time of the crash.
The public affairs office said the Lawrence, the USS Nimitz, USS Princeton, USS Shoup, USS Stockdale and USNS Rainier participated in the search, along with aircraft from HSC-6, Helicopter Maritime Strike Squadron 75 and Patrol Squadron 47.
The crash didn't occur because of hostile activity and an investigation was under way to determine the cause, naval officials said.