The promising 22-year-old, who has managed just three AFL games in four-and-a-half injury plagued seasons with the Blues, contracted his latest and strangest ailment after suffering complications with a troublesome foot.
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It's unknown how long O'Keeffe has carried the infection, but it is believed to have developed after he underwent an operation on his left heel in late 2011.
The infection came to the surface after the Blues' NAB Cup opener against Greater Western Sydney in February.
Further surgery revealed the nature of the problem, which required immediate hospitalisation.
O'Keeffe was initially told he wouldn't play again this season, a terrible prospect for the young man to digest given his seemingly precarious position on the Blues' list.
Three months later, O'Keeffe is still taking antibiotics to rid his system of the infection, but his recovery has so far exceeded expectations.
He is now eyeing a late-season return to the VFL, and hasn’t given up hope of establishing himself as an AFL player.
"I've played at AFL level and I've never felt out of place. I know I can do it. It's just a matter of finally getting that little bit of luck and continuity," he told AFL.com.au.
Sheer football ability was never the issue for O'Keeffe, a powerful defender/midfielder from North Adelaide.
He was one of just three South Australians to be selected in the All Australian Under-18s team of 2008, named on a half-back flank while the likes of Steele Sidebottom and Daniel Rich were listed on the bench.
Among his standout qualities were his hardness and left foot, the one that has since caused him such grief.
Drafted by Carlton with pick 65 in the 2008 draft, O'Keeffe's first season was initially cruelled by osteitis pubis and hip and back problems.
After two seasons he was de-listed without playing an AFL game.
The Blues rookie-listed him for 2011 and it wasn't long before both parties were rewarded for their persistence.
Rhys O'Keeffe taking time out on the couch, with Wilson the dog and his guitar. Picture: AFL Media In round 14, the then 20-year-old made his AFL debut in a six-goal loss to West Coast at Etihad Stadium. He managed eight touches in 42 per cent game time.
Around that time, O'Keeffe's original foot problem flared. His ankle would click when he kicked a ball, and he developed bursitis.
He received painkilling injections to get through the second half of the season, and at year's end underwent surgery to remove a bone spur in his heel that had been rubbing on the Achilles tendon. He also had his tonsils removed and a joint replaced in a finger.
Soon fluid began leaking from a pinprick-sized hole in his heel, which required a clean-out and further stitching.
When O'Keeffe started training again, his foot was so weak from the extended period in a moonboot that it developed stress-related hotspots, which sidelined him for a further 10 weeks.
He returned to the VFL – the Northern Bullants reserves, in fact – midway through the 2012 season. But it was a constant battle.
Training and playing caused the foot to become swollen, which O'Keeffe treated with ice and anti-inflammatories. But he got through, and even cracked it for two AFL games against the Brisbane Lions in round 20 and St Kilda in the final round of the year.
The St Kilda game, O'Keeffe's most recent onfield appearance, has given him mental strength during some seriously trying times.
He was given the job on Brendon Goddard (in Goddard's last game as a Saint) and performed serviceably, having 15 disposals while keeping Goddard to 22 (including a season-low three contested), one goal and no inside-50s.
O'Keeffe learned a lot that day. He noted how hard Goddard ran and worked, and how much help he received from his St Kilda teammates, who "smashed" into the rookie Blue at every opportunity.
That he produced such a creditable performance on limited preparation and under such duress gave him hope.
"It made me wonder what I might do with a full-pre-season behind me. Hopefully I get that chance," he said.
At the end of last season he took just three weeks off before getting back into training because he was desperate to make further inroads under new coach Mick Malthouse.
O'Keeffe joined his teammates at the altitude training camp in Arizona. The foot blew up after hikes, but only to "normal and manageable" levels.
Despite this, he "felt great" and was excited about his prospects.
But he still couldn’t take a trick.
His foot began to swell more than usual after any exertions, and became redder and puffier.
It all came to a head after the Blues' first NAB Cup match at Blacktown, when a lemon-sized mass on his heel split on the original surgery scar and continually oozed fluid.
Strangely, it wasn't painful. In fact, the only thing that stopped O'Keeffe from playing was that it was an open wound and there was a risk of infection. Unbeknownst to anyone at that stage, he was already carrying a bug.
The medicos were perplexed. The wound was injected with dye to see where it led, and it travelled down into his calcaneal (heel bone).
It was the first time doctors considered that he might have an infection. But the heel wasn’t acting like it was infected, and O'Keeffe wasn't ill.
A third operation was needed: a biopsy, in which bone samples were collected and tested.
The surgeons were staggered to find that O'Keeffe was infected with two types of staphylococcus epidermidis (white staph). The danger was that it could travel up his leg and spread to other parts of his body. He needed urgent, ongoing treatment.
"I knew golden staph could be life-threatening, and I was told that one of the white staphs I had was very similar to that, so it was pretty serious," he said.
"Mum and Dad were pretty worried, so they flew over from Adelaide and gave everyone 21 questions to make sure that if I'm not here (at Carlton) next year, that it's not something that will develop again."
O'Keeffe spent a fortnight in hospital, followed by a month in "home hospital": on a couch, hooked up to a drip that pumped antibiotics into him four times a day for an hour at a time. A nurse visited him daily.
As if he hadn’t already endured enough, he then suffered an allergic reaction to the antibiotics. It was the only time he has felt ill throughout the process.
He is grateful for the "amazing support" he has been afforded.
Since he arrived at Carlton he has shared a house with former teammate Jordan Russell, another Adelaide native, who is now with Collingwood. When O'Keeffe was bedridden, Russell and his girlfriend did all the cooking and shopping, and helped him get around.
Carlton's player wellbeing manager Lyndall Down also drove him to medical appointments and collected his antibiotics.
A constant companion on the couch was Russell's dog, a Hungarian Vizsla named Wilson, who gave him great comfort.
O'Keeffe used his idle time to pursue his musical interests – his "escape from footy".
He is teaching himself how to play guitar, and is refining his DJ skills, which he'd previously unleashed at gatherings with friends.
In recent weeks he has also coached the backline for Carlton's VFL affiliate, the Northern Blues.
"It's making me feel part of something," he said.
Several weeks ago he started "real light walking" and gentle stretching, and has progressed to running.
His priorities are to return to full health and fitness, and he is then targeting an appearance in the VFL around round 18.
"But I'd rather have a fully functional foot for the rest of my life than risk coming back too soon," he said.
O'Keeffe has had a cursed run, but he isn’t cursing or complaining. In some ways he actually feels lucky.
"I had the best medical treatment available to me," he said. "If I wasn't on an AFL list, things might have been different; I probably would have kept playing and mightn't have found out about the infection until it was more advanced."
He also consoles himself with the thought that his setbacks have been "insignificant compared to some players". He regards teammate Sam Rowe, who has battled cancer, as an inspiration.
"Sam's great to speak to about staying positive," he said. "After what he went through last year, he's seeing some light at the end of the tunnel. Hopefully I will too."
Ben Collins is a reporter for AFL Media. Follow him on Twitter: @AFL_BenCollins
