Andrea Pirlo is set to make his New York City debut and Frank Lampard could do likewise when their team face Orlando City.
All eyes will be on Yankee Stadium on Sunday with two stars potentially taking the field in MLS for the first time.
Pirlo departed Italy for the United States days ahead of the clash, fresh from his Serie A-winning campaign with Juventus.
Whether the 36-year-old midfield maestro is thrown straight into the New York City team remains to be seen.
Lampard has battled a calf injury, which has delayed his debut, but he is nearing a return to fitness for Jason Kreis' men.
New York City are growing increasingly desperate, sitting second-bottom in the Eastern Conference and three points off sixth-placed Orlando.
While Orlando have been led by nine league goals from Kaka, they have been in a worrying run of form that has included just one win in their past five MLS outings.
Elsewhere, Steven Gerrard and his free-scoring LA Galaxy are at the Houston Dynamo.
Bruce Arena's Galaxy have scored 20 goals in their past five league outings on their way to second in the Western Conference.
The Dynamo are battling in second-bottom in the West, while the Galaxy are only a point behind conference leaders Dallas.
Dallas host the Portland Timbers on Saturday.
Eastern Conference leaders DC United will be out to end a two-game losing league run when they host the Philadelphia Union.
Real Salt Lake and Sporting Kansas City open the latest round of fixtures on Friday, while the Columbus Crew host Toronto, the Seattle Sounders take on the Montreal Impact and the Chicago Fire are at home to the New England Revolution.
Following a loss to Manchester United in the International Champions Cup, the San Jose Earthquakes are at the Vancouver Whitecaps.
