The City full-back is likely to replace Facundo Roncaglia in an Albiceleste side which let a two-goal lead slip in their opening Group B match at the weekend.
Zabeleta had been suffering with an ankle strain but, according to Argentine football journalist Enrique Gastanaga, he has been taking a full part in training and will join Sergio Aguero in the line-up at Estadio La Porta.
Martin Demichelis is expected to continue as an understudy to Ezequiel Garay and Nicolas Otamendi.
Boss Gerardo Martino faced criticism from some sections of the Argentina media for his insistence on an attacking style in the 2-2 draw against Paraguay.
Specifically, the 52-year old’s decision to send on strikers Gonzalo Higuain and Carlos Tevez while his side were clinging onto a narrow 2-1 lead has come under fire.
However, the former Barcelona supremo has indicated that he will stand by his offensive principles against the 15-time South American champions.
“Would I do the same thing again? It’s very difficult to give that answer now,” Martino told reporters in the pre-match press conference on Monday.
“You have a moment to decide. I have a clear idea of the risks, when to take them, when it is convenient and when it is not, and I decided that the quality of Tevez and Higuain could decide the game in our favour.
“The tendency will always be to take risks.
“We are being judged on our second half and not the first and that is our fault: in the first half we played probably the best football of the first round of the Copa America and in the second half we played the worst.”
It’s a crucial game for both Argentina and Uruguay as they both compete for top spot in Group B to avoid fellow favourites Brazil or Colombia until the semi-finals.
Top spot in Group B will mean a quarter-final against one of the best-placed third-placed sides, while second means a clash against Group C’s winners, so there’s plenty on the line when these two old rivals meet.
Uruguay are the only nation to have won more Copa Americas than Argentina and were the side to knock them out four years ago at the quarter-final stage.
Without the suspended Luis Suarez, who will miss the whole competition, Uruguay limped to a 1-0 win over Jamaica in their opening game at the weekend, with Cristian Rodriguez scoring the only goal.
Kick-off in La Serena is at 00:30 (BST) – we’ll have a full report on how the game unfolds here on mcfc.co.uk on Wednesday morning.
Expected Argentina XI: Romero; Zabaleta, Garay, Otamendi, Rojo; Biglia, Mascherano, Pastore; Messi, Aguero, Di Maria
