The Orioles announced that Means has a left elbow strain. Manager Brandon Hyde described the injury as a forearm muscle strain, but said more tests to look at the elbow are forthcoming.
"We don't have much experience in our rotation, and losing your Opening Day starter -- don't know how long it's going to be, but for some time now -- it's going to be hard," Hyde said.
Means, who turns 29 later this month, was pulled after the fourth inning Wednesday night. He's allowed three runs in eight innings in two starts this season.
Last year, Means was a bright spot on a Baltimore staff that ranked last in the majors in ERA. He went 6-9 with a 3.62 ERA and threw a no-hitter at Seattle in May.
The Orioles selected the contract of right-hander Travis Lakins from Triple-A Norfolk, and left-hander Kevin Smith cleared waivers and was assigned to Norfolk.
The Orioles have the top pitching prospect in baseball according to MLB Pipeline: Grayson Rodriguez, who has made two starts at Norfolk this season. However, Hyde said he doesn't expect the injury to Means to affect the promotion timetable for the organization's prospects.
"I would never want to rush a prospect to the big leagues," Hyde said. "When they feel like their prospects are ready, then we're going to welcome them."
Means' IL move is retroactive to Thursday.