Nestor Lorenzo's side will be full of confidence after condemning Brazil to a second consecutive defeat in qualifying for the first time ever.
After what had been a horrific ordeal for the family over the past few weeks, Luis Diaz scored twice with his father in attendance in the win over Brazil, just a week after he was released by kidnappers.
Diaz's goals came late on and within just four minutes of each other as Colombia completed a dramatic turnaround against the five-time world champions.
It was a fully-deserved win for the hosts in Barranquilla, especially after a dominant second-half performance where they outplayed and outfought a rather beleaguered Brazil side.
The win maintains an excellent unbeaten record for Los Cafeteros, extending it to 16 matches - 11 of which have been wins - dating back to February 2022.
Colombia sit third in the CONMEBOL section with nine points after five games and look on course in the early stages to return to the World Cup stage after a shock failure to qualify for the 2022 edition.
Asuncion has been a happy hunting ground for the visitors of late too, as a 1-1 draw in 2021 came after three successive wins for Colombia.
Paraguay have only managed to beat Colombia once on home soil in the 21st century, in a 5-0 thrashing in 2007.
However, it looks highly unlikely that there will be any repeat of that given Paraguay's start, which has not been easy on the eye for the neutrals.
Their five qualifiers so far have produced just three goals - only managing one themselves - after another 0-0 on Thursday in Chile.
There may have been a lack of drama, but that was a very good point for Daniel Garnero's side considering they played over half of the match with 10 men.
The campaign also started with a 0-0 draw, against Peru, which in hindsight looks rather disappointing now, considering that remains their only point in the section so far.
It took four matches for their first goal and their first win, as the draw with Peru was followed by successive 1-0 defeats to Venezuela and Argentina, before eventually getting the better of poor-travellers Bolivia at home.
Paraguay are certainly one of the outsiders to claim an automatic qualifying spot, as they have not shown much might on the continent recently, recording just two wins in their last 14 competitive matches, so that must be improved upon if they want to reach a first World Cup since 2010.
Paraguay's key man Miguel Almiron is not present after becoming the latest addition to the long list of injuries suffered by Newcastle United recently.
Roberto Rojas's first-half red card in Chile means he will be suspended for this clash, meaning another change in personnel is in the offing from manager Garnero, who made numerous alterations to his squad.
Underwhelming performances in October's internationals saw many alterations in the squad picked by the manager, with Hector Villalba, Braian Ojeda, Santiago Arzamendia and Alberto Espinola all left out.
The evergreen Oscar Cardozo has made a comeback to the squad at the age of 40 after two years away though, thanks to his form with domestic club Libertad, where he is having another brilliant year and now has 110 goals since joining in 2017.
Krasnodar striker Jhon Cordoba made his debut off the bench against Brazil last week, but Rafael Santos Borre is in line for another start up front.
Paraguay possible starting lineup:
Carlos; Balbuena, G Gomez, Alderete, Espinoza; Villasanti, Cubas, M Rojas; Sanabria, Cardozo, D Gomez
Colombia possible starting lineup:
Vargas; Munoz, Sanchez, Lucumi, Machado; Castano, Carrascal; Uribe, James, Diaz; Borre
We say: Paraguay 1-1 Colombia
Colombia's unbeaten start has included three draws from five games, including in both of their away games, and it would be no shock to see another tight affair here.
Paraguay battled for a 0-0 in Chile with 10 men, and are slight underdogs here despite home advantage, but they may be able to hold their visitors to a draw here.
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