The shooting was reported around 2:30 a.m. at the Sleepy Hollow Inn in the 24000 block of Lake Drive.
One person was found shot and transported to a hospital.
Two men, identified as Brian Serrano and Jaime Rojas, were arrested after they were seen fleeing the area in a vehicle, the San Bernardino County Sheriff's Department said in a news release.
Serrano, a 43-year-old resident of Sun City, was arrested on suspicion of attempted murder. Rojas, a 46-year-old resident of Santa Ana, will be booked on suspicion of conspiracy to commit attempted murder once he's released from a hospital after suffering unspecified injuries.
The Sheriff's Department said in an earlier news release that two people at the scene were shot, but they did not confirm if Rojas had been injured by gunfire.
Investigators haven't released information on a possible motive in the shooting. They said reports indicated an altercation at the hotel, followed by the shooting. Initial reports on social media indicated a barricaded subject inside the hotel, but investigators said the room turned out to be empty.
The victim has not been identified.
"Everybody's concerned and wondering," said Lisa Scott, a resident of Crestline, who believes she knows who the victim in critical condition is, although it has yet to be confirmed by officials.
"He's quirky, but he's a good guy," said Scott. "He's the kind of guy that if something happens there, he's going to get involved.
"He's not going to stand by and let somebody get hurt on his premises."