Colsaerts, a native of Belgium who had at least a share of the lead after the first and second rounds, ballooned to a 1-over-par 73 in Saturday's third round, while Karlsson, from Sweden, shot a 9-under-par 63.
The pair is 9-under 207 overall.
"I made the mistake of playing on Tuesday, not realizing how much winning had taken out of me," said Karlsson, whose 63 was three shots better then any other player in the field on a day of swirling winds. "And the result was I shot 75 in the first round. Those are the things you have to learn."
Sweden's Jarmo Sandelin (66) is alone in third at 8-under 208.
Four players are tied for fourth at 7-under 209.
South Africa's Richard Sterne is eighth at 6-under 210.
Swim Week Miami Beach 2014 [PHOTOS]