Power and water supply has been badly affected after heavy rains in the state. Search-and-rescue teams used boats and helicopters to pull stranded residents to safety and to try to find residents still missing, authorities said.
Patrick Von Keyserling, an emergency official in Boulder county, an area heavily affected by flooding, said 218 people were unaccounted for.
"That number will fluctuate as families start locating people and as we pick up people that have been stranded with our helicopter operation," he said.
He added that the rescue operations would continue "as the weather is permitting".
"Certainly the intent is to find all unaccountable people. Some may be at rescue centres or staying with relatives," Von Keyserling said.
The floods are the worst to hit Colorado for more than 30 years, and have prompted President Barack Obama to approve a federal disaster assistance request.
Evacuation orders have been issued in several areas, according to a tweet by Colorado Office of Emergency Management.
"The town of Orchard is in immediate danger. EVACUATE NOW," it said. "The town of Goodrich is under an evacuation order."
Motorists were trapped in their cars with emergency crews scrambling to reach them.
"Many, many communities in our western mountains are completely isolated. There is no road access, no telephone information, no power, no water, no sewer," said Sheriff Joe Pelle of Boulder county.
At least four people have been killed, including a couple swept away in floodwaters after stopping their car northwest of Boulder.
Also killed was a resident whose body was found in a collapsed building near Jamestown, an evacuated enclave north of Boulder, and a man whose body was discovered during flood-watch patrols in Colorado Springs, officials said.