The First Stage of the 2011 Copa Santander Libertadores de América ran from January 25 to February 3, 2011 (first legs: January 25–27; second legs: February 1–3).
The twelve teams were drawn into six ties on November 25, 2010 in Asunción.
Teams played in two-legged ties on a home-away basis. Each team earned 3 points for a win, 1 point for a draw, and 0 points for a loss. The following criteria was used for breaking ties on points:
The six winners advanced to the second stage to join the 26 automatic qualifiers.
Team 1 played the second leg at home.