The rules include limiting the distance F-22 planes can travel from airstrips.
Defence Secretary Leon Panetta did not rule out grounding the jets again if necessary.
The Air Force banned its F-22s from flying for four months last year to investigate the oxygen-deficit problem, but its cause remains unclear.
The Air Force has introduced more than a dozen pilot safety rules in the F-22, and says oxygen issues are very rare, but some pilots have refused to fly the aircraft.
The safety precautions announced on Tuesday mean the F-22 will have to abandon long-distance air patrol missions in Alaska, the Pentagon said. The jet has never been used in combat.
Leon Panetta has also asked for a back-up oxygen system to be put into the planes, with the first of these due to be installed in December.
“We haven’t determined the root cause,” Pentagon spokesman George Little said.
“It could be something connected to the oxygen system.
“It could be other aspects of the aircraft that could contribute to hypoxia-like [oxygen-deprivation] events, whether it’s G-forces, the altitude at which the plane flies.”
Twelve hypoxia-related incidents, including dizzy spells and blackouts, have been reported between April 2008 and January 2011.
There are worries that new F-35 fighter jets, which are being developed by Lockheed Martin, could pose similar problems.
“I think it’s safe to say that everybody in leadership is concerned about this,” Pentagon spokesman John Kirby said.
The F-35 will have many of the same features as the F-22, but cannot fly as high or as fast.
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