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Ranked 32nd in the world, he would be the tournament's top seed, as the ranking stood, Tennis SA said in a statement.
"Considering that the Australian Open is played just before our tournament, which makes top-20 players hard to acquire, I feel we've put together a most competitive and interesting field," said tournament director Ian Smith.
"I have little doubt we will be witnessing some remarkable tennis during the first week of February," he said.
The 2011 SA Tennis Open will be played from January 31 to February 6.
Tennis SA said Lopez found the altitude and the faster courts suited his game last year, when his win ended a long drought.
"He is an exciting player to watch and has had some outstanding results this year, notably a straight-sets victory over world number one Rafael Nadal at the Queen's Club at London in June," it said.
Also in the field will be South African Kevin Anderson, who skipped last year. He is ranked 61st in the world.
"It is very exciting for us to have Kevin back for next year's tournament," said Smith.
"The South African public loves to support the local players and with his current form, Kevin is sure to give them something to shout about," he said.
Another player making a return appearance is 2008 finalist Jeremy Chardy, of France, who had to pull out last year because of injury.
All eyes are, however, likely to be on one of the year's most exciting players, Yen-Hsun Lu, of Chinese Taipei, whose ranking rose from 98 to 35 in the course of the year.
"His most memorable performance came at Wimbledon this year where he reached the quarterfinals and took out 2008 finalist Andy Roddick in what some people have called the upset of the year," said Tennis SA.
Lu is coached by German Dirk Hordorff, who is best known for taking Rainer Schuettler into the top 10.
Schuettler, whose world ranking is now 84, is also in the field for the SA Open, as are Frenchman Paul-Henri Mathieu and Serb Janko Tipsarevic.
Just two years ago Mathieu was ranked 12th in the world, but has since dropped to 98.
