Andrew Parish, 28, of Greeley and Martin Cornelio-Hernandez, 51, were both pronounced dead at the scene, troopers said.
The crash occurred at about 9:15 p.m. Saturday, approximately seven miles south of the Wyoming border.
Troopers said Parish was driving a 2004 Chrysler Sebring northbound in the southbound lanes of the highway when he crashed into a 2000 Mazda pickup driven by Cornelio-Hernandez. It isn't clear why Parish was going the wrong way.
Troopers said speed and alcohol are both likely factors in the crash but further details weren't immediately available.