The unthinkable prospect of a World Cup without Argentina or Lionel Messi could move a step closer to becoming reality on Thursday as the South American giants prepare to face arch-rivals Chile in a crucial battle on the road to Russia 2018.
Argentina, who last failed to qualify for the World Cup in 1970, saw their progress towards next year's finals go awry in 2016 when back-to-back draws with Venezuela and Peru were followed by defeats against Paraguay and Brazil.
Although they bounced back to beat Colombia 3-0 in a home qualifier last November, they remain outside the automatic qualifying places in fifth place, with 19 points from 12 games.
A defeat against fourth-placed Chile on Thursday in Buenos Aires would leave Argentina further adrift of the automatic qualifying spots.
And if Colombia beat lowly Bolivia in their home game, as expected, Argentina could even finish the day further down the pecking order, outside of the fifth-place playoff berth they currently occupy.
With a trip to face Bolivia in the thin air of La Paz awaiting them next Tuesday – where Argentina have rarely performed well – it means the two-time World Cup-winners can ill afford to slip up against the Chileans.
Argentina defeated Chile in Santiago earlier in the qualifiers, winning 2-1 in March last year.
However since then Chile inflicted another soul-destroying defeat on the Argentines in a major final, winning the Copa America Centenario final on penalties last June, a year after an identical outcome in the 2015 tournament.
The Copa America Centenario defeat prompted the departure of Gerardo "Tata" Martino as Argentina coach in July, triggering the slump in form which has left their World Cup qualifying campaign in the balance.
The only consolation for new Argentina coach Edgardo Bauza is that opponents Chile are grappling with their own set of problems, notably the suspension of Arturo Vidal and a fitness concern surrounding Arsenal star Alexis Sanchez.
Sanchez trained with the team in Santiago this week despite suffering an ankle injury while on Arsenal duty last weekend.
Brazil on cusp
Thursday's other showpiece game in South America sees Brazil take on Uruguay in Montevideo.
Brazil have transformed their qualifying campaign with six straight victories since new coach Tite took over last year following the Copa America Centenario debacle, where the five-time World Cup winners were eliminated in the group stage.
The Brazilians are now motoring towards qualification for Russia, four points clear at the top of the standings from second-placed Uruguay.
A seventh straight victory on Thursday will all but guarantee Brazil's place at the finals in Russia.
Tite's biggest headache will be attempting to find an adequate back-up to Manchester City starlet Gabriel Jesus, who is injured. Jesus proved to be the catalyst for Brazil's resurgence last year, scoring five goals in six games.
Though there is no obvious like-for-like replacement, Tite still has plenty of attacking options with a strike force led by Neymar.
Liverpool duo Roberto Firmino and Philippe Coutinho could also provide attacking thrust.
Uruguay coach Oscar Tabarez admitted he would have his hands full dealing with Neymar.
Asked how he planned to shackle the Brazil star, Tabarez replied: "If I had a formula I certainly wouldn't share it."
Uruguay also have a problem in attack with Barcelona star Luis Suarez suspended.
That is likely to mean that Edinson Cavani will shoulder the goalscoring threat for Uruguay with support from Diego Rolan.
Elsewhere Thursday, Ecuador will attempt to maintain their place in the automatic qualifying spots as they travel to Asuncion to face Paraguay.
Bottom team Venezuela host Peru.