Aguero missed a penalty as Argentina suffered their first hoe defeat in a World Cup qualifier against Paraguay, losing 1-0 in Cordoba.
Aguero missed the penalty, for the fifth time in 2016, to equalise against Paraguay.
His attempt early in the second half was saved by Justo Villar, who was making his first start since this year’s Copa America.
Paraguay’s winner came after just 18 minutes when winger Derlis Gonzalez outpaced a sluggish defence to score past Sergio Romero.
The loss leaves Argentina in fifth place in the South American qualifying group with 16 points, one point ahead of Paraguay and four behind leaders Uruguay.
The top four go through to the 2018 finals in Russia while the fifth placed team qualifiers for an intercontinental playoff for another berth.
Argentina will be desperate to have a fit Messi back for their next qualifier away to Brazil in Belo Horizonte on November 10.