The midfielder limped off during his country's 1-0 win over South Korea in midweek and is not expected to recover in time for the La Liga showdown.
"The Atletico midfielder retired injured in the encounter between South Korea and Uruguay," read a statement on the Atletico website. "Medical tests have determined he suffered a calf injury in the left leg.
"The player has today undergone medical tests in the FREMAP Majadahonda clinic. The diagnosis has determined that the Uruguayan is also suffering a hamstring injury, which is still being monitored."
Rodriguez has played just six minutes of football for his club this season.