Cooper, who has been sidelined since rupturing an Achilles tendon in Australia's Rugby Championship clash with Argentina earlier this month, has been joined on the sidelines by O'Connor, who was a shock axing following their record loss to the Pumas in the second Test.
O'Connor's place in the squad was taken by 71-Test veteran Bernard Foley, who is in the mix to play five-eighth in Adelaide on Saturday against South Africa.
Cooper had "no doubt" that 32-year-old O'Connor could bounce back, based on his own experience of returning to the Wallabies following five years in exile.
He said he had given the Queensland Reds ace advice to focus on himself rather than the end of goal of returning to the Test fold.
"I said to James your focus can't be solely that your worth is based in being selected in the Wallabies," Cooper told AAP.
"You have to find your worth every day in who you are now, what are the habits, the things you do as a man every day, what you pride yourself on. If they're the right things, they will put you in a good place to be selected for the Wallabies along your own journey.
"So physically, as an athlete, mentally as a man, just continue to work at those and work at it, not to get back into the Wallabies, just for yourself to be better every day.
"When and if you are selected to come back in you will just go about it like it's your every day - that's what held me in a good place."
While Cooper and Foley played in Japan in recent seasons, the fact they were in different divisions means the pair have only met once on the field in recent times.
But Cooper expects the two-time World Cup veteran to be up for the challenge of taking on the world champion Springboks.
Foley, also 32, only joined the Wallabies this week, so youngster Noah Lolesio is more likely to start at five-eighth for the Adelaide Oval Test.
"You never lose your ability so I don't know how he is physically, if he has any injuries or anything like that, but from all accounts he was playing good football in Japan," said Cooper, who was in Melbourne to promote next month's Bledisloe Cup.
"I imagine he's going to slot straight in if he gets an opportunity and it will be great for Noah as well, being around a guy who's been there and done it at the highest level, and will give him a different perspective."
Cooper could see a silver lining in the Wallabies 48-17 loss to the Pumas, which came after a swag of injuries as well as the departure of skipper Michael Hooper from the tour for mental health reasons.
"It was a very young team facing a lot of adversity and losing lot of experience in such a short time," he said.
"But that's how you gain experience, other guys got opportunities so I think that in the long run it's going to be great for the team."
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