Columbus Crewe and Chicago Fire, both featuring Ghanaians, will clash on Saturday
Defenders Jonathan Mensah, Harrison Afful, Lalas Abubakar and midfielder Mohammed Abu all play for Crew, while Chicago Fire features winger David Accam.
Mensah (who joined Crewe in January) and Afful, are widely tipped to start the game for the home side while Accam - one of Fire's best players last season with nine league goals in 21 games - is expected to start for the away side.
The 26-year-old Mensah, who along with 30-year-old Afful was part of Ghana's squad at the recent Africa Cup of Nations in Gabon, has been speaking about the prospect of defending against Accam, who was dropped from the Black Stars squad ahead of the tournament.
"Accam plays with me in the national team and he is a good player. Ghanaians will follow this game closely because we are like brothers and we will face each other. I have received a lot of messages from different people and we cannot wait for the game," Mensah said.
The match kicks off at 7pm Ghana time.