Aguero is injured and Di Maria suspended for a game ahead of which Argentina top the group with 20 points, three ahead of Ecuador.
Coach Alejandro Sabella is understood to be considering Paris St Germain's Ezequiel Lavezzi and Santos' Walter Montillo as the men to replace the absent duo.
Argentina boast the most lethal attack in the South American group with 20 goals in nine games and also hold the best defensive record with seven goals conceded. But Venezuela are the only team to have beaten them so far this campaign.
Argentina's Lionel Messi sounded a note of caution to his team-mates and warned Argentina could not afford another loss to Venezuela.
He said: "When we played there last time we suffered from the heat. This will be a different game, but again a tough one.
"They have a good team, they're balanced and they know what to do on the field," added the Barcelona star.
"But we will go out there and look for the win as we always do. If we achieve it, and we win in Bolivia next week, we will take a great step towards the World Cup."
Venezuela are fourth in the table and are hoping to qualify for their first ever World Cup.
"We go there hoping to make it a great match," said forward Salomon Rondon.
"We don't feel like we are worse than them, we will play them face to face."