The Argentina international had been expected to start the game at the Santiago Bernabeu but was laid low by illness just hours before kickoff.
"Di Maria had to leave Real Madrid training today [Wednesday] due to gastroenteritis," a club statement read. "The Argentine will be out of the match against Borussia Dortmund in the first leg of the Champions League quarterfinals.
"His position will be taken by Jose Rodriguez."
The 26-year-old Di Maria joins left back Marcelo on the sidelines for the Santiago Bernabeu clash.