Del Potro, seventh in the world rankings, said he is still affected by a virus that has limited his play over the last month.
"I am sad to miss such an important tournament, one that you always dream of winning," del Porto said in the withdrawal announcement.
Murray, No. 2 in the rankings, pulled out of the tournament Tuesday, citing a back injury.
"It's a really tough decision and I love playing in Paris," Murray said, "but after seeking medical advice, I am not fit to compete."
Neither has won the French Open but each claimed the U.S. Open -- del Porto in 2009 and Murray last year -- for their first Grand Slam titles.
Mardy Fish and Brian Baker also said they won't be in the draw in Paris. Fish has a heart ailment and Baker is recovering from right knee surgery.
The French Open, with Rafael Nadal seeking a fourth consecutive and ninth overall title, begins Monday.