The midfielder picked up the injury during Real Madrid's 2-1 defeat by Atletico Madrid on Saturday following a heavy challenge from Lee Kang-in. Valverde played on and finished the match, but medical tests later revealed significant damage to his ankle.
Real Madrid confirmed that Valverde has suffered a severe ankle sprain and will undergo further tests to determine how long he will be sidelined.
The injury is understood to be a grade-three sprain, the most serious form of ligament injury, and Spanish media reports have suggested that the 28-year-old could be out for between two and three weeks.
That would rule Valverde out of Uruguay's upcoming matches and could also leave Real Madrid without one of their key midfielders after the international break.
Real Madrid's manager Jose Mourinho was unhappy with the challenge from Kang-in and questioned why it did not result in a penalty or disciplinary action.
Real will now hope Valverde's recovery progresses quickly, with their home match against Villarreal on October 10 viewed as a possible return date.
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