Record seven-times South American champions Independiente dropped to the foot of Group Eight after a 3-1 home defeat by fellow Argentine debutants Godoy Cruz.
Argentine striker Roberto Nanni scored his sixth goal of the competition for Group Five leaders Cerro Porteno in their 1-1 draw at home to Deportivo Tachira of Venezuela in Asuncion.
Velez, who won the Libertadores and world club titles in 1994, lost 2-1 away to Union Espanola, their second defeat to Chilean opposition in successive weeks in Group Four.
At the halfway stage in the group after three matches, Velez have three points, three less than surprise leaders Caracas FC and one behind Espanola and Chilean champions Universidad Catolica.
Martin Liguera shocked Velez with a goal after three minutes and Braulio Leal gave Espanola a two-goal cushion in the 26th minute, heading the ball home after goalkeeper Marcelo Barovero had parried his first effort following a fine run and cross by left back Fernando Cordero.
Velez hit back in the 69th when Uruguayan striker Santiago Silva headed back across goal and midfielder David Ramirez tapped in.
At their Libertadores de America stadium in Buenos Aires Independiente, who won their last of their seven titles in 1984, went ahead after 16 minutes when striker Facundo Parra headed in a free kick.
But an own goal by Hernan Fredes and a 25-metre strike by midfielder Ariel Rojas either side of the half hour put Godoy Cruz in the driving seat. Striker Ruben Ramirez lobbed keeper Hilario Navarro for their third early in the second half.
After three matches, Godoy Cruz and Uruguay's five-times champions Penarol have six points apiece with the Argentines holding the better goal difference. LDU Quito and Independiente have three points each.
