Oakland placed the hard-throwing right-hander on the 15-day DL retroactive to April 3 with a mild subscapularis strain in his right shoulder.
The subscapularis muscle is located underneath the shoulder blade and connects to the front of the upper arm. It works in conjunction with a group of muscles that are used to move the rotator cuff and when injured the subscapularis can cause pain while going through a typical throwing motion.
Harden was scheduled to start Saturday in Cleveland, but after experiencing discomfort in his shoulder during a light toss on Wednesday afternoon, the 26-year-old was forced to cancel his bullpen session and as a result his next outing.
"Harden's not going to be making his next start," Oakland manager Bob Geren said. "He's not going to be ready by that point."
The A's are trying to be as cautious as possible with Harden's latest setback and are taking a wait-and-see approach before setting a throwing plan for his rehabilitation.
"He's going to be given a certain amount of days off and then try to start it back up again," said Geren, prior to Thursday night's finale against the Blue Jays. "We're still talking about exactly how many days would be the right amount. But it definitely won't be today."
Harden first experienced the injury while throwing a bullpen session upon his arrival in the United States following his team's 18-hour flight from Japan at the end of March. In his last outing against Boston on April 2, Harden was forced to leave after just five innings because of inconsistent velocity on his pitches stemming from the shoulder strain.
In two outings this season, Harden is 1-0 with a 0.82 ERA. His 15 strikeouts are second only to Boston's Daisuke Matsuzaka.
His departure from the starting rotation comes as yet another blow to Oakland's pitching staff, which on Tuesday placed right-handed starter Justin Duchscherer on the 15-day disabled list with a strained right biceps muscle.
The A's have yet to name a replacement for Harden's scheduled start on Saturday. The leading candidate, though, appears to be left-handed reliever Lenny Dinardo. The 28-year-old was 7-8 with a 4.93 ERA in 20 starts last season for Oakland.
Geren said the final decision won't come until he sees how much work is needed from his bullpen over the next couple of days.
"[Dinardo's] an option for Saturday," Geren said. "That's one option. What happens during today and tomorrow's game will determine who I use Saturday."
Oakland recalled right-hander Joey Devine from Triple-A Sacramento to take Harden's spot on the 25-man roster. Devine, who was acquired during an offseason deal that sent outfielder Mark Kotsay to Atlanta, has not allowed an earned run in two relief appearances this year.
Last season, Devine combined to go 5-4 with a 1.89 ERA and 20 saves with Double-A Mississippi and Triple-A Richmond in Atlanta's Minor League system.
Gregor Chisholm is a contributor for MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.