With Messi having not played a competitive match in almost a month due to a hamstring problem, Argentina coach Alejandro Sabella opted to start the Barcelona ace on the bench against Colombia and only introduced him around the hour mark.
But even the four-time world player of the year was unable to inspire his side to victory as group leaders Argentina dropped two valuable points, and Sabella must now decide whether Messi will be able to start what promises to be another tough match at altitude against third-placed Ecuador.
Even if he does not feature though, Messi insists his side will go out looking for the win.
"I don't know if I'll play against Ecuador. It was a long time with no footballing activity and playing at high altitude is very demanding," Messi told reporters.
"Anyway, even if I don't play, Argentina will go out for the victory as always."
Ecuador have won all six of their qualifying matches in Quito so far, scoring 13 goals and conceding just twice, and have won three of their last four meetings at home with Argentina.
Argentina also failed to pick up a three-point haul in their trip to high altitude against Bolivia in March, and Sabella is anticipating another tough test in Quito, which is 2,800metres above sea level.
"It's not as high as Bolivia, but we are now playing against a team that is high in the standings," said Sabella, who will be without the suspended Gonzalo Higuain and Pablo Zabaleta.
Argentina defender Jose Maria Basanta is used to playing at altitude during his time with Mexican side Monterrey and he has passed on some advice to his team-mates about how best to cope.
"I've played several times under these conditions and physical matters will be the key. We must be well organised on the field, run intelligently and have the ball possession as much as possible," he said.
Boca Juniors defender Clemente Rodriguez, who has been called up to replace Zabaleta, added: "It won't be easy but we'll go out looking for the victory.
Winning in Ecuador would place us almost at the World Cup."
Despite their draw against Colombia, Argentina moved five points clear at the top of the South American qualifying section on Friday night after nearest challengers Ecuador lost 1-0 at Peru.
That was Ecuador's first defeat on Peruvian soil in 36 years but coach Reinaldo Rueda hopes his side can bounce back quickly.
"We lost and it must make us stronger. The final sprint will not be easy at all. It'll be toughly fought," said Rueda, who will be without the suspended Christian Benitez tomorrow.
On the prospect of Messi not featuring Rueda said: "We are facing a very strong team, with great individual talents.
"However, we must see the group as a whole no matter the individual stars they have."