The aerial search for the 90-year-old man and his 79-year-old wife was halted after officials determined that their chances of surviving in the water were slim, said Chief Warrant Officer Scott Epperson.
"Factoring in their age and weights, their survivability in 59 degrees water was about 4 to 6 hours," he said. "The last time they were seen was 84 hours ago."
The couple were last seen Tuesday aboard the Carnival Paradise.
Officials also consulted with the couple's relatives, who agreed to suspending the search, Epperson said.
Miami-based Carnival said their cabin door was double-locked from the inside with a "Do Not Disturb" sign on the handle. Their belongings remained inside and the door leading from the cabin to the private balcony was unlocked.
Crews searched throughout the night, tracing the route the ship had taken since it left Long Beach on Monday, with stops at Santa Catalina and in Ensenada, Mexico, before returning Friday.
The FBI was investigating, spokeswoman Laura Eimiller said.