Defending champion Louis under 62 on Friday to move atop the leaderboard at the mid point of the Africa Open.
The South African Oosthuizen, who won the 2010 Open Championship, finished 36 holes at 15-under 131 and is two strokes clear at par-73 East London Golf Club.
First-round leader Thomas Aiken managed a four-under 69 on Friday and is tied for second place with two-time U.S. Open champion Retief Goosen (68), Jaco Ahlers (68) and Tjaart van der Walt (64). The group of South Africans finished at minus-13.
Oosthuizen began on the ninth tee Friday, which, instead of the traditional 10th, is used for half of the field due to course logistics. He birdied No. 9, then waited three holes for his next birdie. After a par at 14, Oosthuizen birdied three of his last four to make the turn at nine-under par for the championship.
Oosthuizen did most of his damage on the abbreviated second nine. He birdied the par-five first hole and recorded his next birdie at the next par five, the third. Oosthuizen reached the green in two, but two-putted to get to 11-under par.
At the par-four fifth, Oosthuizen nearly drove the green, then nearly chipped in for eagle. He settled for a birdie and was alone in the lead at 12-under par.
After so many near brushes with eagle, Oosthuizen finally got one at the par- four sixth. He drove the putting surface at the 308-yard hole and drained the 60-footer for eagle.
"It was a lot of concentration on the tee shot because I hit the three-wood in the bush yesterday," explained Oosthuizen. "It was a three-wood again off the tee, and I didn't want to take any other club because I wanted to show myself that I can do it.
"So I hit it on the green at the back. I saw the line of the putt, but I wasn't sure so I asked my caddie and he saw exactly the same line. I hit a perfect putt and it went straight in the middle of the hole. But it was a very long putt, it was probably about 60 feet."
Oosthuizen had one more great putt left in him. At the eighth, his last, the major winner came up 25 feet short with his approach. He holed the curving putt to polish off his 62 and get in with the second-round lead.
"I was aggressive on the putter," said Oosthuizen. "I went about six feet past a few times and I had to make those for par and the last one I made on the eighth would have been eight or 10 foot past, but it hit the middle of the cup.
"But I was aggressive because yesterday I left a few putts short and you're not going to hit it that far past on these greens. I putted brilliantly."
Danny Willett (68), Alastair Forsyth (66), Magnus A. Carlsson (66), Tommy Fleetwood (66) and Craig Lee (67) share sixth place at 11-under 135.
NOTES: Oosthuizen's third European Tour victory after this tournament last year and the Open Championship was the 2010 Open de Andalucia...At 40th, Oosthuizen is the highest-ranked player in the field...The 36-hole cut came at five-under 141 with 82 players making the weekend.