With the Albiceleste facing a difficult home game against rivals Uruguay, any slip would open the door for Ecuador, one point behind, to move ahead or Chile to close a two-point gap to the summit.
The Tricolor will be without suspended Manchester United winger Antonio Valencia, but coach Reinaldo Rueda remains confident of victory in Quito.
"If we maintain the order, the offensive mentality and control the key players of Chile we can win the game," he said.
Chile also have key players missing, with Real Sociedad goalkeeper Claudio Bravo injured and his Primera Division colleague Sevilla's Gary Medel suspended.
Miguel Pinto of Atlas will deputise for Bravo, and coach Claudio Borghi said: "Claudio is a huge player, a big absence for us.
"But I'm confident. We expect to complete a good performance to bring home a good result from Quito."
Colombia, level with Ecuador on 13 points, host rock-bottom Paraguay and can count on the attacking talents of Radamel Falcao, James Rodriguez, McNelly Torres and Teofilo Gutierrez.
But captain Mario Yepes urged caution and said: "Despite their present situation, Paraguay are a very experienced team and I'm sure they will fight until the end.
"They were present at the last four World Cups and that is a fact that we can't forget. To relax would be a huge mistake for us."
Paraguay's Valencia forward Nelson Haedo Valdez admits only victory would keep his team, currently on four points from seven games, in the competition.
"The only result we can accept is a win," he said. "That is the only chance to keep us alive."
Bolivia are languishing on the same total as Paraguay ahead of their clash with fellow strugglers Peru.
With sixth-placed Venezuela not in action in this round of matches, striker Marcelo Moreno is gearing up for a key opportunity to close the gap.
"We have to win," he said. "This match and the following one against Uruguay will define our future."
Despite Peru's three-point advantage over their hosts, coach Sergio Makarian is pessimistic about their prospects in a fixture in which they have traditionally struggled.
"History says that we have never won in La Paz, so I think the fans must be calm," he said.
The following round of matches on Tuesday sees Argentina travel to Chile while Venezuela return to action against Ecuador, Bolivia host Uruguay, Peru face another basement battle against Paraguay and Colombia sit out.