The home side has endured a miserable qualification campaign, with its hopes of making Brazil all but over.
Argentina could end Paraguay's hopes of qualifying for World Cup 2014 when the two sides meet on Tuesday.
The qualification campaign has been poor from start to finish for los Guaranies, who have not recovered from losing six of its first eight matches.
Coach Victor Genes saw his side move off the bottom of the South American group with a convincing 4-0 win over Bolivia on Friday, but the result comes far too late with Paraguay mustering just 11 points from its 13 games to date.
Argentina, on the other hand, has lost just one qualifier in 13 and seven of those games have resulted in wins for the Albiceleste.
Napoli striker Gonzalo Higuain is suspended for this encounter, as is Javier Mascherano, Federico Fernandez and Ezequiel Garay.
But coach Alejandro Sabella has no shortage of replacements, with Manchester City's Sergio Aguero, in-form Inter striker Rodrigo Palacio and PSG's Ezequiel Lavezzi in the squad.
Argentina has not played a competitive match in almost three months, though, with 4-0 and 2-1 friendly wins over Guatemala and Italy filling the schedules in the meantime.
The team was also victorious the last time these sides met, with goals from Angel di Maria, Higuain and Lionel Messi giving it a 3-1 home win in September last year.