The Arizona Republican wants details on the department's plan to retrofit each Raptor with new backup oxygen systems and its decision to limit the type of missions the fighter can fly.
DOD press secretary George Little announced the changes to the Raptor fleet during a Tuesday briefing at the Pentagon.
The changes were made after a scathing report by CBS's "60 Minutes" in which two Air Force pilots claimed problems with the jet's original oxygen system were causing pilots to suffer "psychological incidents" including dizzy spells or blackouts while in flight.
From April 2008 to May 2010, 14 psychological incidents occurred among Air Force pilots flying the Raptor, according to the Air Force.
In March, the Air Force wrapped up a seven-month investigation into those incidents, which forced the service to temporarily ground the entire Raptor fleet twice last year.
Air Force officials could not pinpoint any particular flaw with the jet that would cause the oxygen system to malfunction. That result, coupled with the "60 Minutes" report, prompted Tuesday's announcement.
While Little made clear that flight operations for the Raptor will continue under the new restrictions, McCain pushed the issue in the letter. Specifically, he wanted to know if the plane would still be able to fly missions associated with the Raptor's recent deployment to the Middle East.
"Please describe what effect, if any, these measures will have on the ability of F-22s deployed overseas to execute their intended missions," he said, particularly those in and around the Persian Gulf.
DOD has reportedly begun rotating a squadron of Raptors to Al Dhafra Air Base in the United Arab Emirates. Air Force officials claim the deployments are part of a military partnership program with U.S. allies in the region.
But the American air base in UAE where the Raptors were sent, is stationed alongside the Straits of Hormuz, directly to the south of the Iranian coastline.
On Tuesday, Little confirmed the restrictions on the Raptor would not affect the fighter's Mideast operations. He did not go into details on what those operations entailed.
"In terms of the deployment in southwest Asia, we believe that we can safely continue that deployment given the geography of the region," he told reporters.
The Air Force plans to begin testing on the new backup oxygen system this year, according to Little. Testing is set to wrap up by late November, with installations scheduled to begin by December.
Service officials plan to retrofit 10 jets per month until all 160 fighters are fixed, according to Little.