Lionel Messi's leg injury was the only major obstacle that fell into Argentina's path while it rolled through group play and into the Copa America quarterfinals.

Bigger challenges await the defending champions, and they're hoping Messi will be there to lead the way in perhaps his final international tournament.

The 15-time Copa America champion Albiceleste are still the undeniable favorites in the Americas' biggest soccer tournament when quarterfinal play gets underway, but the other 15-time Copa champs — Uruguay — top the list of challengers capable of taking them down.

With the host Americans and Mexico eliminated in group play, the spotlight shifts firmly to the South American powerhouses determined to raise the trophy.

Argentia vs Ecudaor

In Houston, it's unclear whether Messi will play in the opening quarterfinal due to a leg injury that sidelined him in the team's most recent match against Peru. Coach Lionel Scaloni said Messi's availability will be a game-time decision.

“Depending on how he responds, we will decide,” Scaloni said Wednesday before training. "There are ramifications when Leo is not able to play. We'll try to make sure that he can play. If not, we'll try to find the best solution for the team. I will talk to him today. It's only fair that he can take his time and be able to train as much as he can.”

Argentina has been sturdy even without a goal from Messi in the tournament, winning all three group stage matches by a combined 5-0.

Inter Milan's Lautaro Martinez has four goals in a spectacular effort despite coming off the bench twice, while Manchester City's Julián Álvarez got the other goal. If Scaloni decides to play both center forwards together, it could be more than enough to make up for Messi — and a nightmare for underdog Ecuador, which earned its unexpected quarterfinal spot by holding Mexico scoreless last weekend.

Venezuela vs Canada

In Arlington, Texas, it is a matchup of pleasant surprises. Venezuela has enjoyed an outstanding tournament so far, winning its three matches by a combined 6-1 with offensive leadership from Salomon Rondon and Eduard Bello.

Canada got out of Copa group play for the first time despite scoring just one total goal in three games before losing Inter Milan's Tajon Buchanan to a broken leg in training Tuesday. Reaching the semifinals would be a massive achievement for either of these teams.

Colombia vs Panama

In Glendale, Arizona, the quarters move west for a pair of games held in air-conditioned stadiums amid a continent-wide heat wave.

Colombia is now unbeaten in 26 consecutive matches after holding Brazil to a draw to win its group. Led by veteran star James Rodríguez, Los Cafeteros will be favored to eliminate Panama, which knocked off the host U.S. team to advance from group play.

Brazil vs Uruguay

The Sin City will host easily the most tantalizing matchup of the round, featuring a faltering powerhouse against a team known for perennially punching above its weight.

No quarterfinal team looked as shaky as Brazil, which stumbled into the next round with a thoroughly unimpressive effort. Colombia and Costa Rica both held the Seleçao to draws, and fan discontent is roiling.

Even worse, Real Madrid star Vinicius Junior is suspended for the quarterfinal after accumulating two yellow cards. Yet Brazil is still laden with individual talent that's barely touched the field in this tournament, so it's far too early to write off the five-time World Cup winners.

Uruguay looks just as good as advertised under brilliant coach Marcelo Bielsa, winning three times by a combined 9-1 in group play led by Liverpool striker Darwin Nunez.

After beating Brazil and Argentina in recent World Cup qualifying matches, La Celeste probably would be the tournament favorites if not for Argentina's similarly strong form — but Brazil has the pure talent to end those dreams in a hurry.