Austin Eubanks, who worked as an advocate for fighting addiction, died overnight in the city of Steamboat Springs, Routt County coroner Robert Ryg said.
His cause of death is currently unknown but no foul play is suspected and an autopsy will be carried out on Monday.
Mr Eubanks’ family said he had “lost the battle with the very disease he fought so hard to help others face”.
“We thank the recovery community for its support,” they said in a statement.
“As you can imagine, we are beyond shocked and saddened and request that our privacy is respected at this time.”
Mr Eubanks was 17 when two gunmen entered Columbine High School’s library on 20 April 1999 and opened fire.
The teenager was hit in the hand and the knee during the shooting, in which 13 people were killed, according to The Denver Channel.
At the time the massacre was the deadliest high school shooting in US history.
Mr Eubanks said he became addicted to the painkillers prescribed for his injuries in the aftermath of the shooting.
He later worked at an addiction treatment centre and travelled across the US, telling his story.
“I think that it’s really important that – not as survivors of trauma but survivors of addiction – speak out and they share their story,” he told Denver7 in 2016.
“I remember... hitting multiple low points in my life and thinking there was no way out and I just want people to know there is a way out.”
“Helping to build a community of support is what meant the most to Austin, and we plan to continue his work,” Mr Eubanks’ family said in a statement.
Additional reporting by agencies