The 23-year-old was unsurprisingly called up to Diego Alonso's team for March's friendlies, as Uruguay prepare to meet Japan and South Korea on the 24th and 28th of the month respectively.
Nunez was named in the first XI for Wednesday's Champions League clash with Real Madrid, although a few eyebrows were raised when he came off in the 57th minute.
However, Jurgen Klopp did not report any injury for the former Benfica man, who was expected to play a prominent role for his national team this month.
On Saturday, though, the Uruguayan Football Federation confirmed that Nunez would be forced to withdraw due to injury, being replaced by America forward Jonathan Rodriguez.
Liverpool also confirmed Nunez's latest setback in a statement, which read: "Darwin Nunez has withdrawn from international duty with Uruguay for the upcoming March international break.
"The Liverpool forward had been initially included in his nation's squad for friendly fixtures against Japan and South Korea.
"Nunez will now miss the games due to an injury, as confirmed by the Uruguayan Football Association, and will instead receive treatment at the AXA Training Centre."
No official word has been disclosed on the nature of Nunez's injury, although reports in Uruguay have claimed that the striker is nursing a cut to his ankle.
Liverpool can therefore feel optimistic that Nunez has not suffered anything serious, but news of the striker's issue is hardly welcoming as the Reds try to reignite a top-four charge following the international break.
Nunez has come under fire for wasting a number of gilt-edged chances since his summer move from Benfica, but he has been an integral player for Klopp with 14 goals and four assists from 33 games in all tournaments.
The 23-year-old - who suffered a shoulder injury against Newcastle United last month - has eight goals and three assists to show from 20 Premier League fixtures, and he joins a quintet of players already in the Anfield treatment room.
Calvin Ramsay (knee) and Stefan Bajcetic (adductor) are both missing for the remainder of the season, while Thiago Alcantara and Luis Diaz have also spent time on the sidelines.
However, both men ought to be in contention to return after the international break, where Liverpool will take on reigning Premier League champions Manchester City at the Etihad on April 1.
Last week's 1-0 loss to Bournemouth left Klopp's men sixth in the Premier League table, six points behind fourth-placed Tottenham Hotspur with a game in hand.