Inter Miami rested Lionel Messi and suffered their first defeat since the Argentine joined the club, with a 5-2 hammering at Atlanta United damaging their playoff hopes on Saturday.
Messi had not made the trip to Atlanta, after a busy run of games since making his Miami debut in late July.
Miami coach Gerardo 'Tata' Martino said after the loss that Messi and had been suffering from "muscle fatigue" and that it would have been "very reckless to bring him to play this game".
The 36-year-old had sat out Argentina's World Cup qualifier against Bolivia in La Paz on Tuesday but watched his team-mates from the bench.
Messi was substituted in the final minutes of the 1-0 win over Ecuador on September 7, after scoring the winner, but there have been no reports of an injury.
With no Messi last week, Miami defeated Sporting Kansas City 3-2 but this time it was a very different story for Martino's team.
Miami went ahead in the 25th minute with a superbly taken goal from in-form striker Ecuadorean striker Leonardo Campana .
But the response from Atlanta, sixth in the Eastern Conference, was emphatic with three goals in the space of eight minutes.
The blitz of goals left Miami with plenty to ponder at the interval and they came out strongly, pulling a goal back in the 54th minute.
Miami have made a habit of second-half comebacks in the club's Messi era but lacking the impact of the former Barcelona star they were unable to build sustained momentum.
As they pushed forward in search of an equalizer, Atlanta caught them on the counter.
The break ended with Georgian substitute Saba Lobjanidze squaring to Greek striker Giorgos Giakoumakis who slotted home his 14th goal of the season, bringing him level with Nashville's Hany Mukhtar joint top scorer in MLS.
Another well-worked swift break resulted in the fifth in the 89th minute with Lobjanidze again the creator, setting up Tyler Wolff to blast home.
Miami remain next to bottom of the Eastern Conference, six points behind D.C United who occupy ninth place, the last playoff spot.