Olimpia took a 2-0 lead into the Copa Libertadores final second leg after goals from Alejandro Silva and Wilson Pittoni in the opening match against Atletico Mineiro.
Silva struck in the 22nd minute at Estadio Defensores del Chaco Wednesday with a jinking run and left-footed shot that shook the net after ricocheting off the post, reports Xinhua.
Pittoni doubled the Paraguayan side's lead with a looping free-kick in second-half injury time.
"To give away a goal like that at such a late stage is difficult to take but we can come back from here," said Atletico Mineiro's Brazil international defender Rever.
"We're not going to give up. We'll be playing the next match in front of more than 60,000 fans and with the belief that we can win," he added.
Atletico will be without defenders Richarlyson and Marcos Rocha for next Wednesday's return leg at the Mineirao stadium due to suspension.
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The Brazilian club will be hoping for an improved performance in Belo Horizonte from two-time FIFA world player of the year Ronaldinho, who was benched in the second half here after failing to make an impact.
Olimpia are aiming for their fourth Copa Libertadores title while Atletico have never won South America's most prized club trophy.