Columbus Crew and Inter Miami square off at Lower.com Field on Saturday evening after both teams clinched hard-fought domestic cup victories in midweek.
The hosts are seeking to return to winning ways in MLS, while the visitors hope to avoid a sixth consecutive league setback.
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With a 1-0 victory over Indy Eleven on Wednesday, Columbus Crew advanced to the round of 32 of the US Open Cup.
The lower league opponents appeared to be dragging Wilfried Nancy's team into extra time until Mohamed Farsi broke the tie with seven minutes of normal time remaining.
Prior to that, the Black and Gold were defeated 1-0 by Charlotte FC, dropping them to fifth position in the Eastern Conference.
Inter Miami defeated local rivals Miami FC on penalties in Thursday's US Open Cup match at the Riccardo Silva Stadium.
This followed the Herons' 1-0 loss to the Houston Dynamo, who currently lie bottom, albeit with a game in hand on the three sides just above them.
Following their first away victory in seven attempts last time out, the visitors will look for consecutive wins against enemy territory for the first time since October.
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