Messi has scored 521 goals in 594 games for the Catalan side since making his debut in October 2004.
It is unclear whether Sampaoli will persist with Benedetto again on Tuesday.
This would mean no Lionel Messi to drive television ratings; no Messi to spur ticket sales for local organizers; no Messi to distract from off-field controversies surrounding the world-governing body, FIFA.
Uruguay meanwhile need only take a point in their home qualifier against already-eliminated Bolivia to be certain of progressing. That leaves five teams with varying prospects: Chile (26), Colombia (26), Peru (25), Argentina (25), and Paraguay (24).
In the end, Barca had to make do with Borussia Dortmund's Ousmane Dembele and Gerard Deulofeu, however, the former is injured until the new year.
And if that won't solve it, get set for the drawing of lots.
Multitudinaria marcha en Barcelona para protestar contra independencia de Cataluña
La causa por la unidad española por encima de la independencia catalana reunió a centenares de personas este domingo en diferentes escenarios mundiales.
Nothing has worked so far.
"But in this situation, there is no psychological problem".
Moreover, Argentina face their moment of truth after a series of uninspiring performances that has left the rest of the footballing world scratching its head at how a squad bristling with so much attacking talent has found scoring so difficult.
A loss even leaves the door slightly ajar for a playoff spot. Despite repeated assurances from Barcelona that everything is agreed and settled, and all the formalities simply a matter of time, things have been dragging on.
In news sure to rock Messi, it is claimed the midfielder has told Ronaldo that the Argentina international rules the roost over in Catalonia.
Then, the Blaugrana hierarchy tried desperately to replace the former Santos man and that dragged into yet another theatrical saga with Liverpool's Philippe Coutinho.
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