Kaymer shot a solid two-under-par 70 on Saturday to move to five-under overall, but Oosthuizen closed in on the former world number one with a three-under 69, the joint best round of the day.
Fellow South African Charl Schwartzel is one stroke back after a 70, while two-time defending champion Lee Westwood and rising American star Bill Haas are tied for fourth on two-under-par.
When Oosthuizen made his NGC debut in 2010, he suffered a reaction to eating seafood at the famous beach party at the Valley of the Waves and finished last.
“Two years ago, the whole tournament felt like a blur, I just felt terrible,” Oosthuizen said.
Unbelievably, the South African once again picked up a stomach bug at this year’s beach party and did well to struggle his way to an even-par 72 in the second round.
“Yesterday I wasn’t feeling good at all. Today I still had a bit of cramps and pain in my stomach area, but at least I was able to eat a bit, to get something in me,” Oosthuisen said on Saturday after his round.
The 30-year-old from Mossel Bay produced a skilful display of golf on Saturday, thriving in the tough conditions as sunny skies gave way to cloud and occasional light rain.
“The weather was like on the coast, the wind was all over the place and the ball just didn’t go as far. The rain didn’t do much to make the greens easier either,” Oosthuizen said.
Kaymer, however, is in pole position after recovering from a bogey on the par-four third hole to collect three birdies and not drop another shot.
The German said it had taken him a while to lock down his distance control after a dramatic overnight change in weather.
“It was a bit more difficult than yesterday, especially the first few holes because usually the ball goes a bit further in the heat,” Kaymer said.
“Usually the ball goes 10% further, but it took a while to work out whether it was 10% less today or 5% less. And the wind was swirling around on a few holes too.”
Overnight leader Paul Lawrie’s challenge waned as he struggled to a 75 on Saturday to trail Kaymer by four shots, four bogeys in his first eight holes serving to derail his round.
Schwartzel played some inspired golf, dropping just one shot after a wayward drive on the testing par-four eighth hole as home fans contemplated a first South African triumph in the exhibition event since 2007.