Paraguay can secure a place in the finals for the fourth time in a row if they win or even draw provided Colombia and Ecuador do not win their matches on the same day.
The possibility of Argentina slipping out of the four automatic berths in the South American group looms large after three losses in their last four qualifiers.
Saturday's crushing 3-1 home defeat by Brazil, who secured their place in the 2010 finals in South Africa in the process, was only rendered less damaging by defeats for Ecuador and Uruguay in the places just below Argentina.
One such change could be Estudiantes centre back Rolando Schiavi who could become, at 36 years, seven months and 22 days, Argentina's oldest debutant.
"We must try to profit from Argentina's need to win," said Paraguay defender Julio Cesar Caceres, who plays in Buenos Aires for Boca Juniors.
"If we want to win we must attack but be wary of the quick players Argentina have like Messi because one man alone can't mark him," he told Argentine radio Del Plata.
Paraguay's Argentine coach Gerardo Martino told a news conference on Monday that he could be without goalkeeper and captain Justo Villar, who injured his shoulder in training.
Martino's team are settled even if they have lost the form that took them to the top of the group table last year.
