The Central Americans will be without defender Oscar Bernal and forward Diego Gama, who were red-carded in their shock 2-0 loss against Mali at the weekend.
Gama received a straight red card after dragging Diadie Samassekou down by his collar, while Bernal picked up two yellow cards, one in each half.
Mexico unsuccessfully appealed Bernal's one-match suspension, the mandatory penalty for being sent off.
Speaking at a press conference yesterday, Mexico coach Sergio Almaguer did not hide the fact he disagreed with referee Felix Zwayer's decision to send Bernal off.
''The first red card was OK, the second [player] was a disappointing one. We don't believe it was a correct decision.''
Bernal picked up his second yellow card when he clumsily stuck his left foot out, tripping up a Mali player near the edge of the box.
However, Almaguer accepts he has no choice but to move on without Bernal and Gama against Uruguay, which beat Serbia 1-0 in its opening match at the weekend, and does not think their suspensions will hinder his team.
''It's a team of 21 players; they're all very capable individuals. They will replace the two players that are not able to play. We don't see it as a big problem.''
Mexico trained in Mosgiel yesterday in preparation for the match, which captain Erick Gutierrez sees as a must-win.
''We need to play the game clever,'' he said.
''From my point of view, we need to win this game. Uruguay is a good team but we just need to play and get the best result we can get.''
Uruguay, which beat Serbia despite being outplayed for the majority of the game, has a chance to all but eliminate Mexico from the Fifa Under-20 World Cup.
Coach Fabian Coito said he was expecting Mexico to be less physical than Serbia, but conceded his team needed to play better, including utilising the flanks and not getting too congested in the midfield.
In today's other match, Serbia is also facing a near must-win game against Mali, the surprise group D leader.
The Europeans will still be rueing a number of mixed chances in their loss to Uruguay, a match they probably deserved to at least draw, but will fancy their chances against the West Africans.
Fifa U20 World Cup
Today, Otago Stadium
Mexico v Uruguay, 4pm; Mali v Serbia, 7pm