Sandoval was placed on the 10-day disabled list Tuesday with a sprained right knee. The move is retroactive to Monday, meaning he will be ineligible to return until May 4 at the earliest.
The Red Sox activated infielder Josh Rutledge from the disabled list to take Sandoval's spot on the roster.
"I don't know how long I'll be out," Sandoval said. "Day by day I just want to be consistent every day, be positive that I want to be back as soon as possible. I just want to be 100 percent to do everything I can to help the team win."
Red Sox manager John Farrell said Sandoval's knee is already showing improvement, with the swelling having gone down gradually since Sunday.
The injury comes at a particularly inopportune time, considering shortstop Xander Bogaerts is playing with a sore left thumb, second baseman Dustin Pedroia has missed the past two games with a sore left ankle and left knee and utility infielder Brock Holt is on the disabled list with vertigo.
Rutledge, who figures to split time at third base with lefty-hitting Marco Hernandez in Sandoval's absence, had been sidelined since the final week of spring training with a hamstring strain. Rutledge went 1-for-12 with a home run on a five-game minor league rehab assignment.
Sandoval, who leads the team with three home runs but is hitting .213 this season, was injured Sunday when he dropped down to his knees to stop a hard grounder.