Sergio Busquets was not at Tata Martino's disposal for game two at Mercedes-Benz Stadium when they lost 2-1, with the 2010 World Cup winner dealing with pneumonia and a fever.
He was absent from training on Thursday, just two days before their entire season is on the line, and he is considered doubtful for this weekend too.
Meanwhile, ACL injuries will keep Facundo Farias and Nicolas Freire sidelined for this win-or-go-home encounter against the Five Stripes.
David Martinez seems to have recovered from an adductor strain sustained earlier in the campaign, netting the only goal in their game two defeat.
Ian Fray will not be available because of a meniscus injury, Leo Afonso is doubtful with a sore groin, as are David Ruiz and Oscar Ustari due to hamstring issues.
We expect to see Miami employ a back three once again this weekend with Martinez, Noah Allen and Tomas Aviles all projected to start.
Lately, Jordi Alba has been operating as a wing-back higher up the field on the left side, adding an extra dimension to the attack, and if Busquets cannot go, it will put a lot of pressure on the shoulders of Federico Redondo to contribute in central midfield.
That means Marcelo Weigandt will likely operate once again as a right wing-back in the Herons' starting 11 unless Busquets recovers in time.
Most of the pressure for Miami will be on captain Lionel Messi, a leading candidate to be named the MLS MVP, and their leading goalscorer in the regular season, Luis Suarez.
Earlier this week, Suarez finished second in the race for MLS Newcomer of the Year behind Gabriel Pec of the Los Angeles Galaxy.
Julian Gressel seems to have lost his place in the front three of the attack, with Martino choosing to start Diego Gomez in his place alongside Messi and Suarez for both of their playoff contests.
Robert Taylor played his share of minutes with those two in the early stages of the regular season but has not featured for a single minute in the post-season.
Inter Miami possible starting lineup:
Callender; Aviles, Allen, Martinez; Weigandt, Rojas, Redondo, Alba; Messi, Suarez, Gomez