Major League Soccer outfit Sporting face Real Esteli at home on Wednesday having already inflicted a 2-0 defeat on the Nicaraguan side in the opening game of their 2013-14 campaign back in August.
Toluca of Mexico, meanwhile, travel to Trinidad and Tobago on Thursday to take on a Caledonia AIA team they beat 3-1 last month at Estadio Nemesio Diez.
Miguel Herrera's men lost 1-0 to Costa Rica's Alajuelense courtesy of a late penalty in their last outing, but have the chance to make amends against Sporting San Miguelito at home.
Cruz Azul - the joint-most successful club in the competition alongside America - do not feature in the latest round of fixtures, but could see their Group 3 lead cut when Herediano of Costa Rica host Haiti's Valencia.
Another MLS side, Houston Dynamo, will not play this time around, but will watch intently as their group rivals W Connection of Trinidad and Tobago and Panama's Arabe Unido face off.
Meanwhile, El Salvador's Firpo play host to Victoria of Honduras with both teams chasing a maiden win.
