Both sides are adrift of the top five after disappointing campaigns to this point, but the visitors come into the match on the back of two comfortable victories.
The hosts on the other hand have won just one of their last eight games in all competitions and suffered an embarrassing defeat to Bolivia in the final game of the previous international break.
Their opponents came into the game ninth in the table and 78th in the world - compared to Paraguay's ranking of 38th - but produced a 4-0 thrashing, thanks to goals from Rodrigo Ramallo, Moises Villarroel, Victor Abrego and Roberto Fernandez.
That allowed Bolivia to leapfrog Eduardo Berizzo's side, leaving them eighth with a goal difference of -8.
Time may be running out to rectify this qualification campaign, but the group remains tight enough that two good results in the week's upcoming games could even move them as high as third if results were to go their way.
First, they will have to focus on making amends against a Chile side who beat them 2-0 just under a month ago, but whom they defeated during the three encounters prior to that.
That victory came in an ill-tempered game, which finished with eight yellow cards having been dished out and both sides reduced to 10 men late on.
After over an hour without a goal, Ben Brereton Diaz found the breakthrough to give Chile the lead and Mauricio Isla doubled their lead three minutes later. Charles Aranguiz was then dismissed but his side held firm for the remaining quarter of an hour and saw their task made easier when Paraguay's Omar Alderete also saw red with a few minutes remaining.
Despite having usually been ranked as one of the top 20 teams in the world and having won the Copa America twice in recent years - reaching at least the quarter-finals in all but one of the tournaments since 1999 - Chile's record in qualifying for the World Cup is surprisingly poor.
They have made it to FIFA's showpiece on just three occasions in the last 35 years - in 1998, 2010 and 2014 - finishing sixth in the previous qualification campaign and missing out on a playoff spot via goal difference, despite being just two points behind third-placed Argentina.
La Roja have made it through the group stages at all three of those tournaments, though, before coincidentally being knocked out by Brazil in the round of 16 each time.
They currently sit in that agonising sixth spot once again, but will be determined not to repeat their near-miss of four years ago.
Paraguay centre-back Alderete will be available having served his suspension for the aforementioned red card, but may not immediately return to a back four, with Fabian Balbuena and Gustavo Gomez likely to be the partnership in central defence.
Aranguiz would also be available after serving his suspension but is ruled out of the upcoming international games with a right-calf injury.
The latter's experienced Inter Milan teammate Arturo Vidal will provide the heartbeat of the side from the centre of the park as ever.
Paraguay possible starting lineup:
Silva; Alonso, Gomez, Balbuena, Escobar; Villasanti, Lucena, Sanchez; Almiron, Sanabria, Romero
Chile possible starting lineup:
Bravo; Vegas, Maripan, Medel, Isla; Valdes, Pulgar, Vidal; Sanchez, Jimenez, Brereton Diaz
We say: Paraguay 1-2 Chile
This should be a tight game with both sides desperate for a win, but we are backing Chile to find a crucial edge. They have hit form at a crucial point in the qualifiers whilst their hosts have lost their last two games and should have enough quality and knowhow in the squad to claim all three points.
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