Sporting's manager Peter Vermes has guided his team to the top of the MLS Eastern Conference after 24 matches.
Their latest league outing ended in a comprehensive 4-1 victory over Toronto FC at Sporting Park, with top scorer Dominic Dwyer bagging twice from the penalty spot.
"Everywhere we go we want to get three [points]," Vermes said in the aftermath of the Montreal victory. "Obviously all competitions have different scenarios you're going to be dealing with.
"The first key is we're playing away from home, so we have to be smart there. We've got to be careful not to give goals away, and at the same time, we have to try and capitalise on the mistakes they make."
Defending champions Cruz Azul - who won a record sixth title in April - will look for their first win in Group 6 having limped to a 1-1 draw with Alajuelense in their opening match.
Panamanian Clausura champions Chorrillo provide the opposition this time and they will look to make the most of home advantage against Liga MX's Clausura winners.
DC United start their Champions League campaign on Wednesday, they too have impressed in the MLS Eastern Conference this term and sit second.
Up first for them is a meeting with Waterhouse of Jamaica, who were 2-1 winners over Tauro in their opening Group 4 fixture.
