Early unofficial returns suggested the measure failed in four counties and passed in four, the Fort Collins Coloradoan reported. In another county, early returns showed "yes" votes ahead by a narrow margin, while no results were available for two more.
Backers of the 51st-state initiative suggested the results were getting the message across.
"What we accomplished tonight I believe is a very important discussion," Weld County Commissioner Sean Conway told the newspaper.
Weld was one of the four counties where voters rejected secession.
Most of the counties involved are in the northeastern part of the state and one in the northwest.
Colorado has gone from being a rural state dominated by Republicans to a state where urban and suburban residents in the Denver-Boulder area tend to call the shots. The Democratic governor, John Hickenlooper, and the Democratic majority in the legislature have recently pushed through gun control measures and have even regulated the docking of cattle tails.
"Since nobody is representing the people anyway, it's time that the people stand up and get noticed," said Linda Keener of LaSalle, a small town in Weld County. "The government pushes us aside and doesn't care about us."