The extent of the injuries is likely to be determined Thursday, after both pitchers undergo MRIs. Yet the Giants already realize that they'll be challenged to remain competitive in the National League West if they must endure an extended period without Cain, their No. 2 starter, and Casilla, their top setup reliever.
"It's a huge blow to lose Cain and Casilla," right fielder Hunter Pence said. "Casilla, I think his value to the team is very underrated. He's huge, he's big for us, especially with how many tight ballgames we play."
As Pence spoke, first baseman Brandon Belt dressed in an adjacent locker, providing a reminder of the adversity the Giants already have weathered. The first-place Giants, who lead the Rockies by three games, thus far have survived the absence of Belt, who had a team-high nine homers when he fractured his left thumb May 9.
Manager Bruce Bochy cut short his postgame address to reporters so he and general manager Brian Sabean could discuss replenishing the pitching staff. With Thursday's series finale remaining at Coors Field, where high-scoring games that can decimate a pitching staff are common, Bochy and Sabean likely will want to summon two pitchers immediately.
Cain's injury continued an unlucky year for the three-time All-Star. He recently missed two outings and went on the disabled list with a cut on his right index finger, which occurred while he was making a pregame sandwich April 29 at AT&T Park.
Cain, 29, had performed capably since returning from the DL and was thriving against the Rockies, whom he held hitless for three innings. But on his final pitch of the third inning, a called third strike to Charlie Blackmon, Cain felt a twinge in his hamstring.
"That was the start you wanted to have, especially here," said Cain, who's 1-3 with a 3.66 ERA.
DJ LaMahieu hit a line drive directly back at Cain to open the third inning. But the ball grazed Cain's glove and had nothing to do with the injury.
Any starts Cain misses likely will be inherited by Yusmiero Petit, which was Wednesday night's script. Petit (3-1) duplicated Cain's three shutout innings, allowing only one Colorado runner to reach scoring position.
In contrast to Cain, who strode from the field under his own power, Casilla's injury dampened the mood among many in the Giants' clubhouse, due to the obvious pain he endured.
After rescuing the Giants from a bases-loaded, nobody-out jam in the eighth inning with only one run scoring, Casilla, 33, batted for himself in the ninth and inexplicably approached his at-bat as if the World Series depended on it. Making his fifth career plate appearance with the Giants already ahead by four runs, Casilla faced Boone Logan and worked the count to 3-2 before tapping a grounder to shortstop. Casilla hustled to first base and fell as he crossed the bag, writhing in agony as Bochy and members of the athletic training staff rushed to tend to him.
"I was shocked he was running like that," Bochy said. "I thought he wouldn't even swing. When he hit the ball, I guess he thought he had a hit. I don't know what got into him. I've never seen him run like that."
Casilla, who owns a 1.37 ERA in 22 appearances, has established himself as one of the Giants' most trusted relievers. Jake Dunning, George Kontos or Heath Hembree are among the Triple-A Fresno relievers the Giants could summon to fill Casilla's roster spot. But anybody would be hard-pressed to fill his role.
"We need him," Pence said. "We love having him. But we have a lot of good arms. There's no way to replace him. He's a special arm. He's a special guy. Hopefully it's not too bad of an injury."