Guthrie began running a fever on Sunday and entered the hospital after his temperature started to rise.
"Our doctor felt like it was a form of pneumonia," manager Buck Showalter said after Baltimore beat the Detroit Tigers 5-1 on Monday.
Guthrie was absent at Baltimore's home opener, an indication of just how bad he felt.
"For [Guthrie] not to make the introductions, he is pretty ill," Showalter said. "They are going to keep him overnight tonight."
Guthrie's illness forced Showalter to make yet another adjustment to his starting rotation. Brad Bergesen will start Wednesday in place of Guthrie, whom the Orioles hope to have back on April 10.
Left-hander Brian Matusz, the No. 2 pitcher in the rotation, missed his first start and was placed on the 15-day disabled list with a rib injury.
Guthrie (1-0) started on opening day and blanked Tampa Bay for eight innings in a 4-1 victory. He has been one of the Orioles' most sturdy pitchers over the past four seasons, working in 32 games in 2007, 30 in 2008, 33 in 2009 and 32 last year.
Meanwhile, left fielder Luke Scott was kept out of the starting lineup for a second straight day with a strained groin. The injury occurred Saturday night at Tampa Bay.
He did not play Monday, but Showalter said Scott could have been used as a pinch hitter if necessary.