The Kappa Alpha Psi fraternity annual homecoming party was just getting started when the floor gave way.
Police said some of the attendees broke bones as they fell from the common area into the basement of the off-campus apartment complex.
Emergency responders were at the scene in minutes, and 23 people were taken to hospital.
"The beat was about to drop and literally the whole floor collapsed," student Larissa Stone told Greenville News. "People are hurt. People are bleeding. I had blood on my sneakers. It was really bad."
"Everybody was jumping, next thing you know... I can feel myself falling," attendee Leroy Pearson told local news channel WSPA-TV. "I blacked out, and there [were] girls everywhere with blood all over their face."
University president Jim Clements tweeted that the "entire student support system will be available for any student impacted", and thanked the emergency services for their help.
The university released a statement about the incident, which happened early Sunday morning.
"Clemson Student Affairs is working to determine how many of those injured were Clemson students, and to notify other institutions if one or more of their students were in attendance," it reads.
The building where the party took place at the Woodlands of Clemson apartment complex was reportedly built in 2004. Police said an investigation has begun.
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