The 3rd Marine Aircraft Wing said the CH-53E Super Stallion helicopter was on a routine training mission when it crashed. On it informs TV channel ABC, citing an official statement of the American military.
Naval Air Facility El Centro said in a Facebook post, "We want to thank our friends and neighbors in the Imperial Valley for all of their support and prayers today".
The names of the four crew members presumed killed will be released after their next of kin have been notified.
The crash was under investigation. The helicopter belonged to the 3rd Marine Aircraft Wing in San Diego.
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In total, 13 USA service members have been killed in separate aircraft crashes since March 14: Two Navy aviators died when their F/A-18F Super Hornet crashed off Florida, and seven airmen were killed on March 15 when their Air Force HH-60 crashed in western Iraq, near the Syrian border.
The Sikorsky CH-53E Super Stallion is the largest and heaviest helicopter in the United States military.
Tuesday's crash marks the deadliest crash involving Marines since a year ago. It is primarily used for used for minesweeping and transportation of cargo.
The Latest on a deadly Marine helicopter crash in the California desert.
"No other injuries were reported to personnel on the ground nor damage to infrastructure at the airport", the statement added.