The lions escaped from Kruger National Park on Sunday night and were last seen in the village of Matsulu, South African National Parks said in a statement.
The big cats sneaked out of Kruger park - a major tourist attraction which is nearly the size of Belgium - on Sunday night.
Mabasa says its crucial for communities around the park to contact them immediately if they spot the lions.
"But for now we urge everybody to look out and be cautious for any animals in the area".
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The male lions were believed to have been forced out by a larger pride of lions in the park. "We will continue with this search and use all the necessary resources at our disposal to locate them", said Mr Johannes Nobunga, Chief Executive Officer of MTPA.
In May, the agency captured five lions that broke free from the same park.
The park, which covers an area of 7,523 sq miles and borders Zimbabwe and Mozambique, is home to about 1,500 lions. "Sometimes an entire year passes without lions escaping, and in other years we have a few cases of them escaping", Mabasa said.
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