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.
Another Mexican team, five-time Champions League winners America, are also in action, but are looking to bounce back from a disappointing defeat.
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.
Elsewhere, San Jose Earthquakes will hope to inflict revenge for their 1-0 defeat to MLS rivals Montreal Impact over in Group 5, while LA Galaxy will also stay in the United States to host Isidro Metapan of El Salvador.
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.
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