"It is with great sadness I must announce, I will not be able to participate at this year's Indian Wells tournament due to gastrointestinal issues," she said.
"Those close to me know how much this tournament means to me and how much I wanted to come back and defend my title.
"I would like to thank all the fans who came out here to support me and I am sorry they will not get a chance to see me play this year.
"Now I will rest and recover so I can come out and play and compete for my fans to the best of my abilities once again."
The Russian-born Kazakhstani player won Wimbledon in 2022 and is currently ranked world number four.
She is replaced in the singles draw by lucky loser Kayla Day of the U.S.
Rybakina joins a list of last-minute withdrawals from the tournament including 2021 champion Paula Badosa, who pulled out on Thursday due to an ongoing back injury.
Three-time champion Rafael Nadal withdrew on the eve of his first-round match on Wednesday saying he was not ready to compete at the highest levels.
