Nunez produced an excellent display as Uruguay beat Brazil for the first time in 22 years on Wednesday, scoring the first and assisting the second in a 2-0 win.
But the Liverpool striker came away with concerns over his involvement in the Merseyside derby, partially due to cramping.
“I come to leave everything on the pitch, and today it showed,” he told El Observador. “I ended up a bit cramped at the end.”
This, combined with the long-haul flight back from Uruguay, a lack of recovery and training time plus the early kickoff at Anfield, suggests he will not start.
The availability of Ryan Gravenberch, who was not called up by the Netherlands for so-called disciplinary reasons, makes resting Mac Allister more feasible.
Nunez also picked up a minor concern last month with Uruguay, with manager Marcelo Bielsa bringing him off due to “muscular difficulties.”
The 24-year-old was able to come on for the final 34 minutes of the 3-1 win at Wolves just three days later.